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LOXL2 in Cancer: A Two-Decade Perspective

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Article Gastroenterology & Hepatology

Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma

Marta Alonso-Nocelo et al.

Summary: LOXL2 plays an important role in pancreatic ductal adenocarcinoma (PDAC), with its loss inhibiting metastasis and prolonging overall survival, while overexpression promotes tumor growth and decreases overall survival. Macrophage-secreted OSM is an inducer of LOXL2 expression, with targeting macrophages affecting its expression and collagen fiber alignment.

GUT (2023)

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Article Medicine, Research & Experimental

LOXL2 reduces 5-FU sensitivity through the Hedgehog/BCL2 signaling pathway in colorectal cancer

Zhize Qiu et al.

Summary: This study explored the role of LOXL2 in 5-FU resistance of colorectal cancer (CRC) by analyzing mRNA and protein levels of LOXL2 in public databases, validating it in clinical tissues, and detecting it in 5-FU treated cell lines. Elevated LOXL2 expression was associated with poor prognosis in CRC patients, and it promoted resistance to 5-FU, increased proliferation, and inhibited 5-FU-induced apoptosis in CRC cells. LOXL2 activated the Hedgehog signaling pathway, leading to the upregulation of the anti-apoptotic gene BCL2 in CRC cells. The Hedgehog signaling pathway inhibitor cyclopamine blocked the upregulation of BCL2 mediated by LOXL2. This study demonstrates that LOXL2 reduces 5-FU sensitivity through the Hedgehog/BCL2 signaling pathway in CRC.

EXPERIMENTAL BIOLOGY AND MEDICINE (2023)

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Article Oncology

TRIM44 regulates tumor immunity in gastric cancer through LOXL2-dependent extracellular matrix remodeling

Xin Zhang et al.

Summary: TRIM44 is highly expressed in gastric cancer and is associated with T-cell infiltration. It inhibits gastric tumorigenicity by regulating T-cell-mediated antitumor immunity and modulating the protein level of LOXL2. The TRIM44/LOXL2 complex may serve as a promising biomarker for gastric cancer prognosis and a novel immunotherapy target.

CELLULAR ONCOLOGY (2023)

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Article Gastroenterology & Hepatology

LOXL2 serves as a prognostic biomarker for hepatocellular carcinoma by mediating immune infiltration and vasculogenic mimicry

Nan Zhao et al.

Summary: This study aimed to explore the relationship between LOXL2 and immune infiltration and vasculogenic mimicry (VM) and to identify the role of LOXL2 in HCC diagnosis and prognosis evaluation. The findings showed that LOXL2 expression was higher in HCC than in normal tissues, and high LOXL2 expression was associated with a poorer prognosis of HCC. LOXL2 is involved in immune cell infiltration and promotes VM by upregulating IQGAP1, making it a potential biomarker for HCC diagnosis and prognosis prediction.

DIGESTIVE AND LIVER DISEASE (2023)

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Article Oncology

Hypoxia preconditioned DPSC-derived exosomes regulate angiogenesis via transferring LOXL2

Baoyu Li et al.

Summary: The mechanism of the angiogenic potential in hypoxia-pretreated dental pulp stem cells (DPSCs) was investigated by studying the exosomes secreted by these cells. It was found that these exosomes promote angiogenesis via transfer of lysyl oxidase-like 2 (LOXL2).

EXPERIMENTAL CELL RESEARCH (2023)

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Article Biochemistry & Molecular Biology

Circular RNA PDK1 targets miR-4731-5p to enhance TNXB expression in ligamentum flavum hypertrophy

Kai Zhang et al.

Summary: This study aimed to investigate the role of circular RNAs and microRNAs in the pathogenesis of hypertrophic ligamentum flavum (LF) and lumbar spinal stenosis (LSS), with a focus on circPDK1. The results showed that overexpression of circPDK1 promoted the proliferation, migration, and fibrosis-related protein expression in LF, while miR-4731-5p had opposite effects.

FASEB JOURNAL (2023)

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Article Biochemistry & Molecular Biology

Levoleucovorin inhibits LOXL2 (lysyl oxidase like-2) to control breast cancer proliferation: a repurposing approach

Hemali Deshpande

Summary: This study repurposed FDA approved drugs targeting LOXL2 to control breast cancer progression by using computational screening and in vitro validations. Levoleucovorin was identified as a lead drug candidate to bind to the active site of LOXL2 and inhibit its activity. Further in vitro experiments showed that levoleucovorin significantly inhibited LOXL2 activity and controlled cancer cell proliferation and migration.

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS (2023)

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Article Biochemistry & Molecular Biology

Inhibition of N-glycosylation by glucosamine hydrochloride inhibits TGF-β1-induced LOXL2 secretion

Tetsuro Kamiya et al.

Summary: Kidney fibrosis is associated with chronic kidney disease progression, and LOX enzymes play important roles in regulating extracellular components and facilitating fibrosis. LOXL2 is abundantly expressed in HK2 cells and its inhibition suppresses TGF-beta 1-mediated fibrotic processes. LOXL2 is secreted into the extracellular spaces by exosomes, and Nglycosylation on asparagine residues and N-acetylglucosaminyltransferase 5 are involved in LOXL2 secretion. TGF-beta 1 promotes LOXL2 secretion and may contribute to kidney fibrosis.

JOURNAL OF CELLULAR BIOCHEMISTRY (2023)

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Article Biochemistry & Molecular Biology

New Functions of Intracellular LOXL2: Modulation of RNA-Binding Proteins

Pilar Eraso et al.

Summary: Lysyl oxidase-like 2 (LOXL2) is known as an extracellular enzyme involved in extracellular matrix remodeling, but recent research reveals its intracellular functions in gene transcription, development, differentiation, proliferation, migration, cell adhesion, angiogenesis, and cancer progression. LOXL2 is also capable of inducing epithelial-to-mesenchymal transition (EMT), the first step in metastasis. Through the analysis of LOXL2's nuclear interactome, this study identifies its interaction with numerous RNA-binding proteins (RBPs) involved in RNA metabolism. Gene expression analysis and computational identification of RBPs' targets further suggest six candidates as LOXL2 substrates, warranting future mechanistic analysis. These findings propose novel functions of LOXL2 in tumorigenesis.

MOLECULES (2023)

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Article Multidisciplinary Sciences

The functional and evolutionary impacts of human-specific deletions in conserved elements

James R. Xue et al.

Summary: Disrupted conserved genomic sequences in humans may explain unique human traits. Through analysis, we identified and studied 10,032 human-specific conserved deletions (hCONDELs), which are short deletions that show enrichment for brain functions. By conducting experiments, we found that 800 hCONDELs have significant differences in regulatory activity, with half of them enhancing regulatory function. Some of these hCONDELs are believed to have specific effects on brain development. Restoring an hCONDEL to its ancestral sequence alters the expression of genes involved in myelination and synaptic function. Our findings provide valuable insights into the evolutionary mechanisms driving new traits in humans and other species.

SCIENCE (2023)

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Article Biology

Lysyl oxidase-like 2 processing by factor Xa modulates its activity and substrate preference

Huilei Wang et al.

Summary: This study identifies Factor Xa as a protease involved in the processing of LOXL2, which changes its affinity and substrate preference. Processing by Factor Xa leads to decreased cross-linking activity in the ECM and increased interactions with LOX, indicating a potential compensatory mechanism. This finding has significant implications in diseases where LOXL2 is involved.

COMMUNICATIONS BIOLOGY (2023)

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Review Cell Biology

Lysyl oxidase like-2 in fibrosis and cardiovascular disease

Alan Poe et al.

Summary: This article summarizes the association between LOXL2 and fibrosis and inflammation, examines current therapeutic approaches targeting LOXL2 for fibrosis treatment, and discusses future directions for experiments and biomedical engineering.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2023)

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Article Oncology

Dihydroartemisinin Potentiates VEGFR-TKIs Antitumorigenic Effect on Osteosarcoma by Regulating Loxl2/VEGFA Expression and Lipid Metabolism Pathway

Xiaomin Ding et al.

Summary: Dihydroartemisinin (DHA), a derivative of the Chinese medicine artemisinin, enhances the cytotoxicity of antiangiogenic drugs in osteosarcoma cells by regulating the expression of vascular endothelial growth factor A (VEGFA) and interfering with lipid metabolism.

JOURNAL OF CANCER (2023)

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Article Oncology

Phosphorylation of AKT by lysyl oxidase-like 2 activates the PI3K/AKT signaling pathway to promote proliferation, invasion and metastasis in esophageal squamous carcinoma

Zhiqin Fan et al.

Summary: This study found that LOXL2 promotes the progression of ESCC by regulating the PI3K/AKT signaling pathway. LOXL2 may serve as a clinical warning biomarker or therapeutic target for ESCC.

CLINICAL & TRANSLATIONAL ONCOLOGY (2023)

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Article Oncology

HIF-1α inhibition promotes the efficacy of immune checkpoint blockade in the treatment of non-small cell lung cancer

Fan Luo et al.

Summary: The inhibition of HIF-1 alpha has been found to synergize with anti-PD-1 therapy in impairing tumor growth in NSCLC, enhancing anti-tumor immunity.

CANCER LETTERS (2022)

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Article Cell Biology

LOXL2 small molecule inhibitor restrains malignant transformation of cervical cancer cells by repressing LOXL2-induced epithelial-mesenchymal transition (EMT)

Ting Peng et al.

Summary: This study investigated the expression level and functional mechanism of LOXL2 in cervical cancer using bioinformatics and experimental methods. The results showed that LOXL2 was significantly upregulated in cervical cancer and promoted the malignant transformation of cervical cancer cells through mediation of EMT. Additionally, a small molecule inhibitor of LOXL2 was found to reverse the LOXL2-induced EMT process and decrease the invasive ability of cervical cancer.

CELL CYCLE (2022)

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Article Endocrinology & Metabolism

HucMSCs-exosomes containing miR-21 promoted estrogen production in ovarian granulosa cells via LATS1-mediated phosphorylation of LOXL2 and YAP

Jun-Hong Cai et al.

Summary: This study found that exosomes derived from hucMSCs carrying miR-21 can promote estrogen secretion in ovarian granulosa cells by regulating the phosphorylation levels of LATS1, LOXL2, and YAP.

GENERAL AND COMPARATIVE ENDOCRINOLOGY (2022)

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Article Biochemistry & Molecular Biology

ELK3 Controls Gastric Cancer Cell Migration and Invasion by Regulating ECM Remodeling-Related Genes

Minwook Lee et al.

Summary: The ELK3 gene plays a crucial role in the migration and invasion of gastric cancer cells, and facilitates cancer cell dissemination by modulating extracellular matrix remodeling.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

Loxl2 and Loxl3 Paralogues Play Redundant Roles during Mouse Development

Patricia G. Santamaria et al.

Summary: This study found that the lack of LOXL3 leads to perinatal lethality and abnormal skeletal development in mice, and LOXL2 and LOXL3 may have overlapping functions during mouse development. The widespread expression of LOXL2 can suppress the lethality associated with LOXL3 knockout mice.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

Cleavage of LOXL1 by BMP1 and ADAMTS14 Proteases Suggests a Role for Proteolytic Processing in the Regulation of LOXL1 Function

Tamara Rosell-Garcia et al.

Summary: Members of the lysyl oxidase (LOX) family catalyze the oxidative deamination of lysine and hydroxylysine residues in collagen and elastin. Proteolysis by BMP1 and ADAMTS families regulates LOX enzymes, including LOXL1 associated with pelvic organ prolapse and pseudoexfoliation (PEX) glaucoma. This study reveals the molecular information of LOXL1 proteolysis by BMP1 and ADAMTS14, identifying the processing sites and suggesting complex regulation of LOXL1 function.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Biochemistry & Molecular Biology

Lysyl Oxidase Family Enzymes and Their Role in Tumor Progression

Tanya Liburkin-Dan et al.

Summary: The five genes of the lysyl oxidase family encode enzymes that stabilize the extracellular matrix by cross-linking collagen and elastin. Some of these genes, particularly LOX and LOXL2, are upregulated in hypoxia and promote tumor invasion and metastasis. This review focuses on the molecular mechanisms of lysyl oxidases in tumor progression and the development of inhibitors for cancer treatment and fibrosis-associated diseases.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

Mass Spectrometry-Based Disulfide Mapping of Lysyl Oxidase-like 2

Alex A. Meier et al.

Summary: This study conducted a mass spectrometry-based disulfide mapping analysis to explore the disulfide bond structure of recombinant LOXL2. The results revealed a conserved set of five disulfide bonds in both the precursor and mature forms of LOXL2, while another set of four alternative disulfide bonds, detected in low abundance, was not associated with mature LOXL2.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Obstetrics & Gynecology

LncRNA KCNQ1OT1-mediated cervical cancer progression by sponging miR-1270 as a ceRNA of LOXL2 through PI3k/Akt pathway

Li Jiang et al.

Summary: The KCNQ1OT1/miR-1270/LOXL2 axis modulates the viability and apoptosis of cervical cancer cells.

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (2022)

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Article Oncology

Loxl3 Promotes Melanoma Progression and Dissemination Influencing Cell Plasticity and Survival

Alberto Vazquez-Naharro et al.

Summary: Malignant melanoma is a deadly skin cancer that relies on the phenotypic plasticity of melanoma cells for progression and therapeutic evasion. Loxl3, through regulation of EMT transcription factors such as Snail1 and Prrx1, promotes the progression and metastasis of melanoma, providing a potential therapeutic target.

CANCERS (2022)

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Article Biochemistry & Molecular Biology

Insight into the Spatial Arrangement of the Lysine Tyrosylquinone and Cu2+ in the Active Site of Lysyl Oxidase-like 2

Alex A. Meier et al.

Summary: This study investigates the spatial arrangement of LTQ and the active site Cu2+ in mature LOXL2. The results suggest that LTQ resides within 2.9 angstrom of the active site of Cu2+, and both LTQ and Cu2+ are solvent-exposed.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Medicine, Research & Experimental

Long noncoding RNA HCP5 promotes osteosarcoma cell proliferation, invasion, and migration via the miR-29b-3p-LOXL2 axis

Jin-Dian Tan et al.

Summary: The lncRNA HCP5 upregulates LOXL2 expression by targeting miR-29b-3p, thereby promoting the proliferation, migration, and invasion of osteosarcoma.

KAOHSIUNG JOURNAL OF MEDICAL SCIENCES (2022)

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Article Neurosciences

GDNF Promotes Astrocyte Abnormal Proliferation and Migration Through the GFRα1/RET/MAPK/pCREB/LOXL2 Signaling Axis

Miaomiao Wang et al.

Summary: High concentrations of GDNF can enhance the proliferation and migration ability of astrocytes, leading to the malignant transformation into astroglioma cells. This process is mediated by the activation of LOXL2 expression and secretion, which remodels the extracellular microenvironment and promotes abnormal astrocyte proliferation and migration.

MOLECULAR NEUROBIOLOGY (2022)

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Article Pharmacology & Pharmacy

Lysyl Oxidases Expression and Breast Cancer Progression: A Bioinformatic Analysis

Sofia Ramos et al.

Summary: LOX and LOXL1-4 are enzymes that catalyze the cross-linking of elastin and collagen, potentially facilitating breast cancer metastasis. This study explores the role of each LOX in breast cancer and finds that LOXL2 is an important biomarker and therapeutic target, while LOXL3 and LOXL4 have different expression profiles compared to LOX, LOXL1, and LOXL2.

FRONTIERS IN PHARMACOLOGY (2022)

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Article Oncology

Inhibitory effects of LOXL2 knockdown on cellular functions of liver cancer stem cells

Na Li et al.

Summary: The study found that LOXL2 inhibitors can reduce the proliferation and expansion of liver cancer stem cells and induce apoptosis and cell cycle arrest. These results provide a promising avenue for novel therapeutic strategies for HCC.

TRANSLATIONAL CANCER RESEARCH (2022)

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Article Multidisciplinary Sciences

L2Δ13, a splicing isoform of lysyl oxidase-like 2, causes adipose tissue loss via the gut microbiota and lipid metabolism

Yang Chen et al.

Summary: This study found that overexpression of L2 Delta 13 in mice resulted in lower body weight, accompanied by changes in gut microbiota and abnormal lipid metabolism. L2 Delta 13 may impact lipid uptake and adipose tissue homeostasis, leading to weight loss and reduced adipose tissue area.

ISCIENCE (2022)

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Article Oncology

Loss of LOXL2 Promotes Uterine Hypertrophy and Tumor Progression by Enhancing H3K36ac-Dependent Gene Expression

Xufeng Lu et al.

Summary: In this study, LOXL2 was found to play a role in the epigenetic regulation of tumorigenesis and cancer progression, specifically in the female reproductive system. LOXL2 restricts cancer development through the deacetylation of H3K36ac. LOXL2 loss promotes uterine cancer initiation and progression, and represses the efficacy of anti-PD-1 immunotherapy.

CANCER RESEARCH (2022)

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Article Biochemistry & Molecular Biology

A 3D-Predicted Structure of the Amine Oxidase Domain of Lysyl Oxidase-Like 2

Alex A. Meier et al.

Summary: This study generated a 3D-predicted structure of the C-terminal amine oxidase domain of LOXL2 and discussed the active site environment surrounding LTQ and Cu2+.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Cell Biology

LncRNA CARMN Affects Hepatocellular Carcinoma Prognosis by Regulating the miR-192-5p/LOXL2 Axis

Xiaokang Wang et al.

Summary: This study found that CARMN may be the potential upstream lncRNA for the hsa-miR-192-5p/LOXL2 axis in HCC. Additionally, the level of LOXL2 is significantly positively associated with tumor immune cell infiltration and immune checkpoint expression in HCC.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2022)

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Review Genetics & Heredity

Crosstalk between Hypoxia and Extracellular Matrix in the Tumor Microenvironment in Breast Cancer

Yasmin Dekker et al.

Summary: This review studies the crosstalk between hypoxia and the extracellular matrix (ECM) in breast cancer. The findings suggest that hypoxia directly contributes to ECM remodeling, alters cell metabolism, and is regulated by the YAP/TAZ mechanotransduction pathway. The review highlights the importance of understanding these interactions for breast cancer progression.

GENES (2022)

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Article Biochemistry & Molecular Biology

LOXL2-dependent deacetylation of aldolase A induces metabolic reprogramming and tumor progression

Ji-Wei Jiao et al.

Summary: The study reveals that LOXL2 and its L2A13 variant can enhance glucose metabolism, cell proliferation, and tumor development in esophageal cancer. Additionally, LOXL2 and L2A13 directly activate glycolytic enzymes, leading to metabolic reprogramming and tumor progression.

REDOX BIOLOGY (2022)

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Article Biochemistry & Molecular Biology

Matrix stiffness-mediated effects on macrophages polarization and their LOXL2 expression

Xiaoxia Xing et al.

Summary: The study showed that increased matrix stiffness significantly enhanced M2 macrophage polarization and promoted LOXL2 expression. Activation of the integrin beta 5-FAK-MEK1/2-ERK1/2 pathway contributed to matrix stiffness-mediated HIF-1 alpha upregulation, leading to a significant improvement in LOXL2 expression.

FEBS JOURNAL (2021)

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Article Obstetrics & Gynecology

Lysyl oxidase like protein-2 (LOXL-2); a novel marker for prediction of intrahepatic cholestasis of pregnancy

Ugur Turhan et al.

Summary: The study found that maternal serum levels of LOXL-2 were significantly higher in women with ICP, and were positively correlated with FTBA levels. LOXL-2 may serve as both an initiating factor in the pathophysiology of ICP and a predictive marker, and could be a target for prevention strategies in ICP.

JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE (2021)

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Article Cell Biology

Reciprocal regulation of LOXL2 and HIF1α drives the Warburg effect to support pancreatic cancer aggressiveness

Rongkun Li et al.

Summary: This study identifies a previously unknown hypoxia-LOXL2-HIF1α axis that regulates the Warburg effect in PDAC, providing a potential drug target for therapy. LOXL2 plays a crucial role in stabilizing HIF1α and promoting glycolytic metabolism under hypoxia, linking the Warburg effect to tumor growth and metastasis in PDAC. Hijacking glycolysis compromises LOXL2-induced oncogenic activities in this context.

CELL DEATH & DISEASE (2021)

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Article Multidisciplinary Sciences

Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis

Divya Ramchandani et al.

Summary: Copper chelation reduces TNBC metastasis by inactivating Complex IV in sensitive SOX2/OCT4+ cells, showing potential to enrich patient populations in next-generation therapeutic trials.

NATURE COMMUNICATIONS (2021)

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Review Oncology

Targeting Lysyl Oxidase Family Meditated Matrix Cross-Linking as an Anti-Stromal Therapy in Solid Tumours

Yordanos F. Setargew et al.

Summary: The lysyl oxidase (LOX) family of enzymes play a key role in the formation of desmoplastic matrix in both primary tumors and secondary metastatic sites. With the growing interest in anti-stromal therapies, the LOX family has emerged as a potential clinical target. This review explores how dysregulation of the lysyl oxidase family in solid cancers contributes to disease progression, as well as the potential use of the LOX family as diagnostic and prognostic markers in solid tumors.

CANCERS (2021)

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Review Biochemistry & Molecular Biology

LOXL2 Inhibitors and Breast Cancer Progression

Sandra Ferreira et al.

Summary: LOX and LOXL2 are amine oxidases that catalyze cross-linking reactions of elastin and collagen in connective tissue, with LOXL2 showing high expression in certain tumors. Inhibition of LOX and LOXL2 is considered a promising strategy for preventing metastasis and invasion of breast cancer. Novel synthetic compounds acting as selective inhibitors for LOX/LOXL2 or dual LOX/LOXL inhibitors have been developed, showing potential for effective therapeutic approaches in breast cancer treatment.

ANTIOXIDANTS (2021)

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Article Biochemistry & Molecular Biology

Oligomeric States and Hydrodynamic Properties of Lysyl Oxidase-Like 2

Alex A. Meier et al.

Summary: LOXL2 is a promising therapeutic target against metastatic/invasive tumors and organ and tissue fibrosis by promoting crosslinking of proteins in the ECM. The study found that while fl-LOXL2 predominantly exists as a monomer, Delta 1-2SRCR-LOXL2 exists solely as a monomer.

BIOMOLECULES (2021)

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Letter Oncology

An activity-based bioprobe differentiates a novel small molecule inhibitor from a LOXL2 antibody and provides renewed promise for anti-fibrotic therapeutic strategies

Alison Findlay et al.

CLINICAL AND TRANSLATIONAL MEDICINE (2021)

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Article Genetics & Heredity

LOXL4 Abrogation Does Not Exaggerate Angiotensin II-Induced Thoracic or Abdominal Aortic Aneurysm in Mice

Huimin Li et al.

Summary: The LOXL4 gene may not play a major role in the development of TAAD, as shown by the findings from a study using a knockout mouse model. Functional studies using animal models are crucial for evaluating candidate genes identified in WES for TAAD.

GENES (2021)

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Article Biochemistry & Molecular Biology

MIR29A Impedes Metastatic Behaviors in Hepatocellular Carcinoma via Targeting LOX, LOXL2, and VEGFA

Ya-Ling Yang et al.

Summary: This study demonstrates the inhibitory effect of MIR29A on LOX, LOXL2, and VEGFA by targeting their 3' UTRs, leading to promotion of apoptosis and reduction in cell viability and wound healing. The results confirm that MIR29A-3p mimic can directly bind to the 3' UTRs of LOX and VEGFA to downregulate their gene and protein expression levels.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Cell Biology

Targeted Deletion of Loxl3 by Col2a1-Cre Leads to Progressive Hearing Loss

Ziyi Liu et al.

Summary: Research shows that the lack of Loxl3 in the inner ear may lead to hearing loss, hair cell degeneration, and neuronal degeneration, indicating that Loxl3 plays a crucial role in maintaining auditory function.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Article Biotechnology & Applied Microbiology

Circular RNA circ_0000228 promotes the malignancy of cervical cancer via microRNA-195-5p/lysyl oxidase-like protein 2 axis

Shimei Liu et al.

Summary: Circular RNAs play a crucial role in cervical cancer by promoting cancer progression through sponging miR-195-5p and up-regulating LOXL2 expression.

BIOENGINEERED (2021)

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Article Oncology

Novel mechanism for OSM-promoted extracellular matrix remodeling in breast cancer: LOXL2 upregulation and subsequent ECM alignment

Simion C. Dinca et al.

Summary: High co-expression of LOXL2 and OSM in IDC patients is associated with worse metastasis-free survival rates, while high levels of either individually are less impactful; LOXL2 expression is positively correlated with OSM/OSM receptor (OSMR) expression in IDC patients. Additionally, OSM-induced LOXL2 promotes an increase in ECM collagen I fiber crosslinking, leading to significant fiber alignment between cells and increased IDC cell invasion.

BREAST CANCER RESEARCH (2021)

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Article Medicine, Research & Experimental

LOXL2-enriched small extracellular vesicles mediate hypoxia-induced premetastatic niche and indicates poor outcome of head and neck cancer

Guiquan Zhu et al.

Summary: Research shows that sEVs derived from the hypoxic tumor microenvironment of HNSCC can drive local invasion of non-hypoxic HNSCC cells and stimulate premetastatic niche formation by delivering LOXL2 to non-hypoxic HNSCC cells and fibroblasts to induce EMT and fibronectin production, respectively.

THERANOSTICS (2021)

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Article Biochemistry & Molecular Biology

Salidroside ameliorated hypoxia-induced tumorigenesis of BxPC-3 cells via downregulating hypoxia-inducible factor (HIF)-1α and LOXL2

Xiaoping Chen et al.

JOURNAL OF CELLULAR BIOCHEMISTRY (2020)

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Article Medicine, Research & Experimental

Elevated exosomal lysyl oxidase like 2 is a potential biomarker for head and neck squamous cell carcinoma

Tomoyoshi Sanada et al.

LARYNGOSCOPE (2020)

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Article Chemistry, Medicinal

2-Aminomethylene-5-sulfonylthiazole Inhibitors of Lysyl Oxidase (LOX) and LOXL2 Show Significant Efficacy in Delaying Tumor Growth

Deborah A. Smithen et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

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Article Biochemistry & Molecular Biology

LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells

J. P. Cebria-Costa et al.

ONCOGENE (2020)

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Article Biochemistry & Molecular Biology

Scavenger Receptor Cysteine-Rich domains of Lysyl Oxidase-Like2 regulate endothelial ECM and angiogenesis through non-catalytic scaffolding mechanisms

Claudia Umana-Diaz et al.

MATRIX BIOLOGY (2020)

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Article Oncology

miR-29a Is Repressed by MYC in Pancreatic Cancer and Its Restoration Drives Tumor-Suppressive Effects via Downregulation of LOXL2

Shatovisha Dey et al.

MOLECULAR CANCER RESEARCH (2020)

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Article Oncology

Identification and characterization of the promoter of cancer-related gene LOXL2

Xin Liu et al.

EXPERIMENTAL CELL RESEARCH (2020)

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Article Oncology

LOXL2 Expression Status Is Correlated With Molecular Characterizations of Cervical Carcinoma and Associated With Poor Cancer Survival via Epithelial-Mesenchymal Transition (EMT) Phenotype

Canhui Cao et al.

FRONTIERS IN ONCOLOGY (2020)

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Article Oncology

LOXL2 promotes oncogenic progression in alveolar rhabdomyosarcoma independently of its catalytic activity

Olga Almacellas-Rabaiget et al.

CANCER LETTERS (2020)

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Review Gastroenterology & Hepatology

Lysyl Oxidase (LOX) Family Members: Rationale and Their Potential as Therapeutic Targets for Liver Fibrosis

Wei Chen et al.

HEPATOLOGY (2020)

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Review Cell Biology

Guidelines and definitions for research on epithelial-mesenchymal transition

Jing Yang et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2020)

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Article Cell Biology

Wnt signaling and Loxl2 promote aggressive osteosarcoma

Kazuhiko Matsuoka et al.

CELL RESEARCH (2020)

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Article Medicine, Research & Experimental

Pancreatic ductal adenocarcinoma progression is restrained by stromal matrix

Honglin Jiang et al.

JOURNAL OF CLINICAL INVESTIGATION (2020)

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Review Biochemistry & Molecular Biology

Linking LOXL2 to Cardiac Interstitial Fibrosis

Melisse Erasmus et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Article Oncology

Comprehensive analysis on the expression levels and prognostic values of LOX family genes in kidney renal clear cell carcinoma

Shitong Lin et al.

CANCER MEDICINE (2020)

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LOXL2 Upregulation in Gliomas Drives Tumorigenicity by Activating Autophagy to Promote TMZ Resistance and Trigger EMT

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ADVANCED THERAPEUTICS (2020)

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Structures of SALSA/DMBT1 SRCR domains reveal the conserved ligand-binding mechanism of the ancient SRCR fold

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LIFE SCIENCE ALLIANCE (2020)

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GINS2 promotes cell proliferation and inhibits cell apoptosis in thyroid cancer by regulating CITED2 and LOXL2

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CANCER GENE THERAPY (2019)

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Simtuzumab for Primary Sclerosing Cholangitis: Phase 2 Study Results With Insights on the Natural History of the Disease

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Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin

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LOXL2-A New Target in Antifibrogenic Therapy?

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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

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Prognostic and clinicopathological significance of LOXL2 in cancers: A systematic review and meta-analysis

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Specific protein 1(SP1) regulates the epithelial-mesenchymal transition via lysyl oxidase-like 2(LOXL2) in pancreatic ductal adenocarcinoma

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Mechanism for oral tumor cell lysyl oxidase like-2 in cancer development: synergy with PDGF-AB

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Lysyl Oxidase-Like Protein 2 Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer

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Extracellular ATP promotes breast cancer invasion and epithelial-mesenchymal transition via hypoxia-inducible factor 2α signaling

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LOXL2 Upregulates Phosphorylation of Ezrin to Promote Cytoskeletal Reorganization and Tumor Cell Invasion

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Lysyl oxidases: from enzyme activity to extracellular matrix cross-links

Sylvain D. Vallet et al.

EXTRACELLULAR MATRIX (2019)

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The lysyl oxidase like 2/3 enzymatic inhibitor, PXS-5153A, reduces crosslinks and ameliorates fibrosis

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Lysyl oxidase-like 2 is a regulator of angiogenesis through modulation of endothelial-to-mesenchymal transition

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MiR-504 inhibits cell proliferation and invasion by targeting LOXL2 in non small cell lung cancer

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Simtuzumab Is Ineffective for Patients With Bridging Fibrosis or Compensated Cirrhosis Caused by Nonalcoholic Steatohepatitis

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Matrix stiffness-upregulated LOXL2 promotes fibronectin production, MMP9 and CXCL12 expression and BMDCs recruitment to assist pre-metastatic niche formation

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Crystal structure of human lysyl oxidase-like 2 (hLOXL2) in a precursor state

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

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The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2

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NATURE COMMUNICATIONS (2018)

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Hepatitis transactivator protein X promotes extracellular matrix modification through HIF/LOX pathway in liver cancer

Aki Pui-Wah Tse et al.

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Upregulation of MIAT Regulates LOXL2 Expression by Competitively Binding MiR-29c in Clear Cell Renal Cell Carcinoma

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Extracellular Processing of Lysyl Oxidase-like 2 and Its Effect on Amine Oxidase Activity

Kazushi Okada et al.

BIOCHEMISTRY (2018)

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The serum level and significance of lysyl oxidase-like 2 in patients with rheumatoid arthritis-associated interstitial lung disease

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CLINICAL RHEUMATOLOGY (2018)

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Lysyl oxidase-like 3 is required for melanoma cell survival by maintaining genomic stability

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CELL DEATH AND DIFFERENTIATION (2018)

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Influencing the Tumor Microenvironment: A Phase II Study of Copper Depletion Using Tetrathiomolybdate in Patients with Breast Cancer at High Risk for Recurrence and in Preclinical Models of Lung Metastases

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CLINICAL CANCER RESEARCH (2017)

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Regulation of metastasis-promoting LOXL2 gene expression by antitumor microRNAs in prostate cancer

Mayuko Kato et al.

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The histone demethylase KDM4B regulates peritoneal seeding of ovarian cancer

C. Wilson et al.

ONCOGENE (2017)

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Proteolytic processing of lysyl oxidase-like-2 in the extracellular matrix is required for crosslinking of basement membrane collagen IV

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Fibroblast-specific inhibition of TGF-β1 signaling attenuates lung and tumor fibrosis

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Identification of 4-(Aminomethyl)-6-(trifluoromethyl)-2-(phenoxy)pyridine Derivatives as Potent, Selective, and Orally Efficacious Inhibitors of the Copper-Dependent Amine Oxidase, Lysyl Oxidase-Like 2 (LOXL2)

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Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation

Li Ma et al.

MOLECULAR CELL (2017)

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A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab in Combination with FOLFIRI for the Second-Line Treatment of Metastatic KRAS Mutant Colorectal Adenocarcinoma

J. Randolph Hecht et al.

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Small Molecule Lysyl Oxidase-like 2 (LOXL2) Inhibitors: The Identification of an Inhibitor Selective for LOXL2 over LOX

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ACS MEDICINAL CHEMISTRY LETTERS (2017)

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Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancer

Joan Chang et al.

ONCOTARGET (2017)

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Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden

Zachary R. Chalmers et al.

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Efficacy of simtuzumab versus placebo in patients with idiopathic pulmonary fibrosis: a randomised, double-blind, controlled, phase 2 trial

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LANCET RESPIRATORY MEDICINE (2017)

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LOXL2 drives epithelial-mesenchymal transition via activation of IRE1-XBP1 signalling pathway

Eva P. Cuevas et al.

SCIENTIFIC REPORTS (2017)

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Increased serum lysyl oxidase-like 2 levels correlate with the degree of left atrial fibrosis in patients with atrial fibrillation

Yingming Zhao et al.

BIOSCIENCE REPORTS (2017)

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Lysyl Oxidase-like Protein LOXL2 Promotes Lung Metastasis of Breast Cancer

Fernando Salvador et al.

CANCER RESEARCH (2017)

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A phase 2 study of simtuzumab in patients with primary, post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis

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BRITISH JOURNAL OF HAEMATOLOGY (2017)

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Sex-Linked Skeletal Phenotype of Lysyl Oxidase Like-1 Mutant Mice

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CALCIFIED TISSUE INTERNATIONAL (2016)

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Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma

Keiko Mizuno et al.

INTERNATIONAL JOURNAL OF ONCOLOGY (2016)

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Tumor-suppressive microRNAs (miR-26a/b, miR-29a/b/c and miR-218) concertedly suppressed metastasis-promoting LOXL2 in head and neck squamous cell carcinoma

Ichiro Fukumoto et al.

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Tumor Cell Invasion Can Be Blocked by Modulators of Collagen Fibril Alignment That Control Assembly of the Extracellular Matrix

Moran Grossman et al.

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Lysyl Oxidase, a Targetable Secreted Molecule Involved in Cancer Metastasis

Thomas R. Cox et al.

CANCER RESEARCH (2016)

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Localized LoxL3-Dependent Fibronectin Oxidation Regulates Myofiber Stretch and Integrin-Mediated Adhesion

Ortal Kraft-Sheleg et al.

DEVELOPMENTAL CELL (2016)

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TGF-β1 promotes linear invadosome formation in hepatocellular carcinoma cells, through DDR1 up-regulation and collagen I cross-linking

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EUROPEAN JOURNAL OF CELL BIOLOGY (2016)

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Lysyl Oxidase Isoforms and Potential Therapeutic Opportunities for Fibrosis and Cancer

Philip C. Trackman

EXPERT OPINION ON THERAPEUTIC TARGETS (2016)

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Lysyl oxidase-like 2 (LOXL2) oxidizes trimethylated lysine 4 in histone H3

Nicolas Herranz et al.

FEBS Journal (2016)

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SMYD3 stimulates EZR and LOXL2 transcription to enhance proliferation, migration, and invasion in esophageal squamous cell carcinoma

Ying Zhu et al.

HUMAN PATHOLOGY (2016)

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Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma

Akira Kurozumi et al.

INTERNATIONAL JOURNAL OF ONCOLOGY (2016)

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Simtuzumab treatment of advanced liver fibrosis in HIV and HCV-infected adults: results of a 6-month open-label safety trial

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LIVER INTERNATIONAL (2016)

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Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment

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NATURE COMMUNICATIONS (2016)

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Escin Ia suppresses the metastasis of triple-negative breast cancer by inhibiting epithelial-mesenchymal transition via down-regulating LOXL2 expression

Yuhui Wang et al.

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Loss of Lysyl Oxidase-like 3 Attenuates Embryonic Lung Development in Mice

Jian Zhang et al.

SCIENTIFIC REPORTS (2016)

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Lysyl oxidase-like 2 represses Notch1 expression in the skin to promote squamous cell carcinoma progression

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Tumour-suppressive microRNA-29s directly regulate LOXL2 expression and inhibit cancer cell migration and invasion in renal cell carcinoma

Rika Nishikawa et al.

FEBS LETTERS (2015)

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Loss of lysyl oxidase-like 3 causes cleft palate and spinal deformity in mice

Jian Zhang et al.

HUMAN MOLECULAR GENETICS (2015)

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LOXL2 Oxidizes Methylated TAF10 and Controls TFIID-Dependent Genes during Neural Progenitor Differentiation

Ane Iturbide et al.

MOLECULAR CELL (2015)

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Origin and evolution of lysyl oxidases

Xavier Grau-Bove et al.

SCIENTIFIC REPORTS (2015)

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Lysyl oxidase-like 2 (LOXL2) and E47 EMT factor: novel partners in E-cadherin repression and early metastasis colonization

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Human copper-dependent amine oxidases

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ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS (2014)

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Lysyl oxidase-like 2 (LOXL2) controls tumor-associated cell proliferation through the interaction with MARCKSL1

Boh-Ram Kim et al.

CELLULAR SIGNALLING (2014)

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67 laminin receptor promotes the malignant potential of tumour cells up-regulating lysyl oxidase-like 2 expression in cholangiocarcinoma

Jing Xu et al.

DIGESTIVE AND LIVER DISEASE (2014)

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Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression

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EUROPEAN RESPIRATORY JOURNAL (2014)

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Lysyl Oxidase-Like 2 Is Critical to Tumor Microenvironment and Metastatic Niche Formation in Hepatocellular Carcinoma

Carmen Chak-Lui Wong et al.

HEPATOLOGY (2014)

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Peptides derived from the copper-binding region of lysyl oxidase exhibit antiangiogeneic properties by inhibiting enzyme activity: an in vitro study

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JOURNAL OF PEPTIDE SCIENCE (2014)

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LOXL2 Status Correlates with Tumor Stage and Regulates Integrin Levels to Promote Tumor Progression in ccRCC

Hiroaki Hase et al.

MOLECULAR CANCER RESEARCH (2014)

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Lysyl oxidase (LOX) in vascular remodelling

Mar Orriols et al.

THROMBOSIS AND HAEMOSTASIS (2014)

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LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition

Eva P. Cuevas et al.

BIOLOGY OPEN (2014)

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An Impermeant Ganetespib Analog Inhibits Extracellular Hsp90-Mediated Cancer Cell Migration that Involves Lysyl Oxidase 2-like Protein

Jessica McCready et al.

CANCERS (2014)

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Lysyl oxidase-like-2 promotes tumour angiogenesis and is a potential therapeutic target in angiogenic tumours

Shelly Zaffryar-Eilot et al.

CARCINOGENESIS (2013)

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MCF-7 Cells Expressing Nuclear Associated Lysyl Oxidase-like 2 (LOXL2) Exhibit an Epithelial-to-Mesenchymal Transition (EMT) Phenotype and Are Highly Invasive in Vitro

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Tumor-Secreted LOXL2 Activates Fibroblasts through FAK Signaling

Holly E. Barker et al.

MOLECULAR CANCER RESEARCH (2013)

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Regulation of Heterochromatin Transcription by Snail1/LOXL2 during Epithelial-to-Mesenchymal Transition

Alba Millanes-Romero et al.

MOLECULAR CELL (2013)

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The Cancer Genome Atlas Pan-Cancer analysis project

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Regulatory networks defining EMT during cancer initiation and progression

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NATURE REVIEWS CANCER (2013)

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LOXL2 induces aberrant acinar morphogenesis via ErbB2 signaling

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Cancer-associated fibroblasts up-regulate CCL2, CCL26, IL6 and LOXL2 genes related to promotion of cancer progression in hepatocellular carcinoma cells

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BIOMEDICINE & PHARMACOTHERAPY (2012)

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The Enzymatic Activity of Lysyl Oxidas-like-2 (LOXL2) Is Not Required for LOXL2-induced Inhibition of Keratinocyte Differentiation

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JOURNAL OF BIOLOGICAL CHEMISTRY (2012)

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Epithelial to Mesenchymal Transition Is Activated in Metastatic Pheochromocytomas and Paragangliomas Caused by SDHB Gene Mutations

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Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2012)

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LOXL2-Mediated Matrix Remodeling in Metastasis and Mammary Gland Involution

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CANCER RESEARCH (2011)

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Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas

Gema Moreno-Bueno et al.

EMBO MOLECULAR MEDICINE (2011)

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Receptor activity modifying protein-3 mediates the protumorigenic activity of lysyl oxidase-like protein-2

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Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2011)

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Epithelial-Mesenchymal Transition Induced by Hepatitis C Virus Core Protein in Cholangiocarcinoma

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ANNALS OF SURGICAL ONCOLOGY (2010)

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The Lysyl Oxidases LOX and LOXL2 Are Necessary and Sufficient to Repress E-cadherin in Hypoxia INSIGHTS INTO CELLULAR TRANSFORMATION PROCESSES MEDIATED BY HIF-1

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Modulation of Lysyl Oxidase-like 2 Enzymatic Activity by an Allosteric Antibody Inhibitor

Hector M. Rodriguez et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2010)

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Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment

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Secreted LOXL2 is a novel therapeutic target that promotes gastric cancer metastasis via the Src/FAK pathway

Liang Peng et al.

CARCINOGENESIS (2009)

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1,25(OH)2D3 regulates collagen quality in an osteoblastic cell culture system

Hideaki Nagaoka et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2008)

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Lysyl oxidase-like 2 as a new poor prognosis marker of squamous cell carcinomas

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CANCER RESEARCH (2008)

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VE-statin/egfl7 regulates vascular elastogenesis by interacting with lysyl oxidases

Etienne Lelievre et al.

EMBO JOURNAL (2008)

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Snail, ZEB and bHLH factors in tumour progression: an alliance against the epithelial phenotype?

Hector Peinado et al.

NATURE REVIEWS CANCER (2007)

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Switching on-off snail -: LOXL2 versus GSK3β

H Peinado et al.

CELL CYCLE (2005)

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A molecular role for lysyl oxidase-like 2 enzyme in Snail regulation and tumor progression

H Peinado et al.

EMBO JOURNAL (2005)

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Elastic fiber homeostasis requires lysyl oxidase-like 1 protein

XQ Liu et al.

NATURE GENETICS (2004)

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Lysyl oxidase is required for vascular and diaphragmatic development in mice

IK Hornstra et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2003)

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Inactivation of the lysyl oxidase gene Lox leads to aortic aneurysms, cardiovascular dysfunction, and perinatal death in mice

JM Mäki et al.

CIRCULATION (2002)

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Review Medicine, Research & Experimental

Copper control as an antiangiogenic anticancer therapy: Lessons from treating Wilson's disease

GJ Brewer

EXPERIMENTAL BIOLOGY AND MEDICINE (2001)

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Multiple bone morphogenetic protein 1-related mammalian metalloproteinases process pro-lysyl oxidase at the correct physiological site and control lysyl oxidase activation in mouse embryo fibroblast cultures

MI Uzel et al.

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