☆ 4.3 Review

CCN proteins: opportunities for clinical studies-a personal perspective

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2023)

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Article Biochemistry & Molecular Biology

The ADAM9/WISP-1 axis cooperates with osteoblasts to stimulate primary prostate tumor growth and metastasis

An-Chen Chang et al.

Summary: This study found that primary prostate cancer cells expressing ADAM9 protein can transform osteoblasts into prostate cancer-associated osteoblasts (PCa-OBs) and induce the secretion of WISP-1 in the bone microenvironment. Elevated levels of WISP-1 promote aggressive behavior of prostate cancer cells through epithelial-mesenchymal transition (EMT). Targeting the ADAM9/WISP-1 axis may be a potential therapeutic strategy for preventing the malignant progression of prostate cancer cells.

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES (2023)

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The carboxyl-terminal TSP1-homology domain is the biologically active effector peptide of matricellular protein CCN5 that counteracts profibrotic CCN2

Sima Zolfaghari et al.

Summary: Cellular Communication Network (CCN) proteins play important roles in cellular responses associated with organ development and tissue homeostasis. CCN5, a divergent member of the CCN family, releases the TSP1 homology domain as its bioactive signaling entity, and inhibits key signaling pathways stimulated by CCN2. Moreover, the CCN5 TSP1 domain also inhibits cell migration and scratch wound closure induced by CCN1/2.

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Article Cell Biology

CCN3/NOV promotes metastasis and tumor progression via GPNMB-induced EGFR activation in triple-negative breast cancer

Seogho Son et al.

Summary: In this study, the overexpression of CCN3 in TNBC patients was found to be associated with unfavorable outcomes. CCN3 knockdown reduced cancer stem cell formation, metastasis, and tumor growth by inhibiting the EGFR/MAPK pathway. Furthermore, CCN3 was found to activate the Wnt signaling pathway, leading to increased expression of GPNMB.

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Do not overwork: cellular communication network factor 3 for life in cartilage

Satoshi Kubota et al.

Summary: CCN3, as a founding member of the CCN family, has diverse functions and generally represses cell proliferation. It plays a critical role in cartilage metabolism by restricting energy consumption and promoting chondrocytes' quiescence and survival. CCN3 also has important functions in articular cartilage maintenance and skeletal development.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2023)

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The role of CCNs in controlling cellular communication in the tumor microenvironment

Lauren B. Birkeness et al.

Summary: The Cellular communication network (CCN) family of growth regulatory factors are a group of secreted proteins that promote signal transduction through cell-cell or cell-matrix interaction. Each protein has specific functions in healthy and cancer biology, regulating cell adhesion, proliferation, migration, invasiveness, apoptosis, and survival. Understanding the microenvironment of each protein can lead to a better understanding of interactions and signaling cascades.

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CCN6 influences transcription and controls mitochondrial mass and muscle organization

Ananya Ganguly et al.

Summary: This study reveals a new function of CCN6 in transcriptional regulation. It shows that CCN6 localizes to chromatin and associates with RNA Polymerase II. Using zebrafish as a model, the nuclear presence of CCN6 and its association with RNA Polymerase II are validated, and the requirement of CCN6 in the transcription of genes encoding mitochondrial electron transport complex proteins is confirmed.

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Editorial Material Cell Biology

Time has come to address the spatiotemporal combinatorial model for CCN proteins biological activitites by spatial transcriptomics and genome wide association studies

Bernard Perbal

Summary: We wish our authors, editorial board members, and readership a happy new year and predict that 2023, the Year of Water Rabbit, will be a quiet year for assessing and planning the future of our Journal. We present here a summary of necessary CCN research directions that require collaborative approaches.

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The matricellular protein CCN3 supports lung endothelial homeostasis and function

Kalpana R. Betageri et al.

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Binding of the angiogenic/senescence inducer CCN1/CYR61 to integrin α6β1 drives endocrine resistance in breast cancer cells

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Cell Communication Network factor 4 promotes tumor-induced immunosuppression in melanoma

Audry Fernandez et al.

Summary: Cell Communication Network factor 4 (CCN4/WISP1) is a matricellular protein secreted by cancer cells that promotes metastasis by inducing the epithelial-mesenchymal transition. Knocking out CCN4 reduces tumor growth and increases tumor-infiltrating leukocytes, natural killer cells, and CD8(+) T cells in immunocompetent mice. CCN4 suppresses IFN-gamma release by CD8(+) T cells and enhances tumor secretion of chemokines that attract myeloid-derived suppressor cells. CCN4 KO potentiates the anti-tumor effect of immune checkpoint blockade therapy.

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Connective tissue growth factor expression hints at aggressive nature of colorectal cancer

Ishrat Parveiz Bhat et al.

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WORLD JOURNAL OF GASTROENTEROLOGY (2022)

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Tissue distribution and transcriptional regulation of CCN5 in the heart after myocardial infarction

Sima Zolfaghari et al.

Summary: CCN5 primarily exists in endothelial cells, fibroblasts, and macrophages in differentiating scar tissue in the heart, and its transcription is inversely regulated by beta(2)-adrenergic agonists and TNF-alpha. It antagonizes the profibrotic actions of CCN2 and inhibits myocardial collagen deposition and fibrosis in chronic pressure overload of the heart.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2022)

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Targeting CCN2 protects against progressive non-alcoholic steatohepatitis in a preclinical model induced by high-fat feeding and type 2 diabetes

Jing Ren et al.

Summary: This study investigates the pathogenic role of CCN2 protein in NASH pathology and identifies it as a molecular target in NASH with high fat diet and diabetes. The regulation of ERK signaling is implicated in this process.

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The matricellular protein CCN6 differentially regulates mitochondrial metabolism in normal epithelium and in metaplastic breast carcinomas

Mai Tran et al.

Summary: The study found that CCN6 plays a critical role in regulating redox states during the progression of MBC. Downregulation of CCN6 leads to abnormal expression of mitochondrial respiratory chain genes, affecting cell survival. This research provides a new direction for potential preventative and treatment strategies against MBC based on CCN6 upregulation.

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Multifunctional regulatory protein connective tissue growth factor (CTGF): A potential therapeutic target for diverse diseases

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Autophagic degradation of CCN2 (cellular communication network factor 2) causes cardiotoxicity of sunitinib

Zhifei Xu et al.

Summary: Excessive macroautophagy induced by sunitinib leads to apoptosis of cardiomyocytes and cardiac dysfunction through the TOLLIP-mediated endosome-related pathway. Additionally, deletion of Hmgb1 or treatment with the HMGB1-specific inhibitor glycyrrhizic acid can significantly mitigate sunitinib-induced autophagy, cardiomyocyte death, and cardiotoxicity. This study reveals a novel target protein of autophagic degradation in the regulation of cardiomyocyte death and suggests HMGB1 inhibition as a promising strategy for enhancing the safety of sunitinib-based cancer therapy.

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Extracellular ATP promotes angiogenesis and adhesion of TNBC cells to endothelial cells via upregulation of CTGF

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Molecular and Genetic Interactions between CCN2 and CCN3 behind Their Yin-Yang Collaboration

Satoshi Kubota et al.

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Understanding Human Epidermal Stem Cells at Single-Cell Resolution

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WISP-2 modulates the induction of inflammatory mediators and cartilage catabolism in chondrocytes

Clara Ruiz-Fernandez et al.

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Circulating Levels of WISP-1 (Wnt1-Inducible Signaling Pathway Protein 1) and Other Selected Adipokines in Children With Inflammatory Bowel Disease

Eva Karaskova et al.

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The TSP-1 domain of the matricellular protein CCN5 is essential for its nuclear localization and anti-fibrotic function

Min Ho Song et al.

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PLOS ONE (2022)

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Article Immunology

CCN1 Promotes Inflammation by Inducing IL-6 Production via α6β1/PI3K/Akt/NF-κB Pathway in Autoimmune Hepatitis

Renquan Jiang et al.

Summary: This study found that CCN1 was over-expressed in hepatocytes of patients with autoimmune hepatitis (AIH). Serum CCN1 level also increased in AIH patients compared to healthy controls. Conditional knockout of CCN1 reduced inflammation in a ConA-induced hepatitis mouse model. CCN1 treatment induced IL-6 production in LO2 cells and this production was attenuated by CCN1 knockdown. CCN1 could activate IL-6 production via the PI3K/Akt/NF-kappa B signaling pathway.

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WISP2/CCN5 Suppresses Vasculogenic Mimicry through Inhibition of YAP/TAZ Signaling in Breast Cancer Cells

Nathalie Ferrand et al.

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Article Cardiac & Cardiovascular Systems

Matricellular Protein CCN5 Gene Transfer Ameliorates Cardiac and Skeletal Dysfunction in mdx/utrn (±) Haploinsufficient Mice by Reducing Fibrosis and Upregulating Utrophin Expression

Min Ho Song et al.

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Data Mining Identifies CCN2 and THBS1 as Biomarker Candidates for Cardiac Hypertrophy

Markus Johansson et al.

Summary: This study compares the gene expression patterns of an in vitro stem cell-based cardiac hypertrophy model with biopsies collected from hypertrophic human hearts. It identifies differentially expressed genes and corresponding secreted proteins, highlighting the role of CCN2 in cardiac hypertrophy. The study also reveals biological processes associated with cardiac function and the development of cardiac hypertrophy. These findings contribute to the identification of potential biomarkers for cardiac hypertrophy.

LIFE-BASEL (2022)

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Microglia and Brain Macrophages as Drivers of Glioma Progression

Yuqi Zheng et al.

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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Multidisciplinary Sciences

Suppression of choroidal neovascularization and epithelial-mesenchymal transition in retinal pigmented epithelium by adeno-associated virus-mediated overexpression of CCN5 in mice

Sora Im et al.

Summary: This study suggests that CCN5 may provide a potential novel strategy for the treatment of neovascular age-related macular degeneration (nAMD). The researchers found that rAAV2-CCN5 attenuated CNV lesions and angiogenesis in a mouse model, and also normalized morphological defects in retinal pigmented epithelium (RPE) cells. In addition, rAAV2-CCN5 blocked fibrotic deformation through inhibiting epithelial-mesenchymal transition (EMT).

PLOS ONE (2022)

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WISP1 induces ovarian cancer via the IGF1/αvβ3/Wnt axis

Yan Li et al.

Summary: This study aimed to clarify the mechanisms by which WISP1-mediated IGF1/alpha v beta 3/Wnt axis affects the progression of ovarian cancer. The expression of IGF1 and WISP1 was elevated in ovarian cancer tissues and cells, which correlated with poor prognosis. Elevated IGF1 induced malignant properties of ovarian cancer cells through activation of PI3K-Akt and Wnt signaling pathway. WISP1 enhanced the interaction between IGF1 and alpha v beta 3 to induce epithelial-mesenchymal transition. In vivo experiments confirmed that upregulated WISP1/IGF1 induced tumorigenesis and metastasis of ovarian cancer cells.

JOURNAL OF OVARIAN RESEARCH (2022)

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Chitosan Nanoparticles: A Versatile Platform for Biomedical Applications

Showkeen Muzamil Bashir et al.

Summary: Chitosan is a versatile natural polymer with biodegradable and biocompatible properties. It has been extensively explored in various biomedical applications, including wound treatment, nanocarriers, and tissue-engineering scaffolds. The antibacterial, antioxidant, and haemostatic properties of chitosan make it an excellent option for wound dressings, and its hydrophilic nature makes it an ideal starting material for biocompatible and biodegradable hydrogels.

MATERIALS (2022)

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Article Cell Biology

Silencing the Adipocytokine NOV: A Novel Approach to Reversing Oxidative Stress-Induced Cardiometabolic Dysfunction

Maayan Waldman et al.

Summary: This study investigates the interaction between adipose tissue-specific NOV/CCN3 and cardiometabolic function. Inhibiting NOV expression improves adipose tissue function, cardiac metabolism, and mitochondrial function in obese mice, resulting in improved glucose tolerance, decreased inflammation, and improved cardiovascular function.

CELLS (2022)

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Potential Role of Polyphenolic Flavonoids as Senotherapeutic Agents in Degenerative Diseases and Geroprotection

Kingsley C. Mbara et al.

Summary: Cellular senescence, a hallmark of ageing, contributes to tissue or organ dysfunction and the pathophysiology of diverse age-related diseases (ARD) by various mechanisms. Targeting it by selective elimination of senescent cells (SCs) or blocking senescence-associated secretory phenotypes (SASP) with natural or synthetic compounds has been suggested to improve lifespan.

PHARMACEUTICAL MEDICINE (2022)

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Evolution of metastasis: new tools and insights

Philippe Gui et al.

Summary: This review summarizes the latest genetic and lineage-tracing approaches developed to unravel the genetic evolution of metastasis. The findings have enhanced our understanding of the mechanistic trajectories and timescales of metastasis and could potentially provide new strategies for therapy.

TRENDS IN CANCER (2022)

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The Role of CCN1 in Esophageal Adenocarcinoma: What We Have Learned From the Lab

Zhiheng Chang et al.

Summary: This article provides a summary of the laboratory work on the role of CCN1 in esophageal cancer and offers a new perspective on CCN1 biology. The study revealed that CCN1 induces TRAIL-mediated apoptosis in esophageal cancer cells, and antagonizes the effects of TNF. These findings suggest that CCN1 has the potential to be a candidate for the treatment of esophageal cancer.

CANCER CONTROL (2022)

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Article Cell Biology

Blocking CCN2 preferentially inhibits osteoclastogenesis induced by repetitive high force bone loading

Mary F. Barbe et al.

Summary: Blocking CCN2 signaling reduces trabecular bone catabolism induced by high repetition high force tasks, leading to decreased bone resorption and improved bone volume.

CONNECTIVE TISSUE RESEARCH (2021)

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Article Cardiac & Cardiovascular Systems

Diabetes Promotes Retinal Vascular Endothelial Cell Injury by Inducing CCN1 Expression

Haicheng Li et al.

Summary: This study identified CCN1 as an important regulator in the pathogenesis of DR. Increased expression of CCN1 stimulates oxidative stress and disrupts tight junction integrity in endothelial cells. Targeting the CCN1/NOX4 axis provides a therapeutic strategy for treating DR by alleviating endothelial cell injury.

FRONTIERS IN CARDIOVASCULAR MEDICINE (2021)

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Cellular senescence in ageing: from mechanisms to therapeutic opportunities

Raffaella Di Micco et al.

Summary: Cellular senescence is characterized by permanent proliferation arrest and can occur in response to various stresses like telomere dysfunction. Apart from stress-induced senescence, it can also be part of controlled programs in biological processes like embryonic development. Senescent cells contribute to impaired tissue regeneration, chronic diseases, and organismal aging, but also present an opportunity for intervention in aging and associated diseases.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2021)

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Review Biochemistry & Molecular Biology

Metabolic Effects of CCN5/WISP2 Gene Deficiency and Transgenic Overexpression in Mice

Tara Alami et al.

Summary: CCN5/WISP2 is a matricellular protein regulated by Wnt signaling and IGF-1, playing a role in promoting pancreatic beta-cell proliferation and survival while affecting adipocyte development and metabolic regulation. Experimental results showed that CCN5 deficiency led to adipocyte hypertrophy and insulin resistance, while overexpression increased lean body mass and improved insulin sensitivity. Further research is needed to explore other aspects of CCN5 physiology.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Cell Biology

CCN2 (Cellular Communication Network factor 2) in the bone marrow microenvironment, normal and malignant hematopoiesis

Roos J. Leguit et al.

Summary: CCN2, also known as Connective Tissue Growth Factor, is a matricellular protein that modifies signaling activity and orchestrates cross-talk in various signaling pathways. It is involved in regulating multiple biological processes, including cell proliferation, differentiation, migration, survival, apoptosis, and extracellular matrix production. In the bone marrow, CCN2 is crucial for mesenchymal stem cell function and supports hematopoietic stem cells maintenance and lymphocyte differentiation. Overexpression of CCN2 has been linked to fibrosis and certain types of cancer, particularly in leukemias.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2021)

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Review Cell Biology

The CCN2/CTGF interactome: an approach to understanding the versatility of CCN2/CTGF molecular activities

Viktor Zaykov et al.

Summary: CCN2/CTGF is a multifunctional protein that regulates diverse cellular processes including adhesion, proliferation, apoptosis, and extracellular matrix synthesis, with different effects on developmental and pathological processes. It interacts with cell surface receptors, growth factors, and ECM proteins to elicit various cellular responses, highlighting its complexity and tissue-specific effects. Discovery of new binding partners may provide insights into unknown roles of CCN2/CTGF for potential therapeutic targeting.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2021)

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Review Biochemistry & Molecular Biology

Role of Matricellular CCN Proteins in Skeletal Muscle: Focus on CCN2/CTGF and Its Regulation by Vasoactive Peptides

Daniela L. Rebolledo et al.

Summary: The CCN family of matricellular proteins plays crucial roles in cell signaling pathways, particularly in skeletal muscle physiology and disease. They are involved in regulating muscle mass, maintaining vascularization, and modulating skeletal muscle fibrosis.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Targeting CCN Proteins in Rheumatoid Arthritis and Osteoarthritis

Iona J. MacDonald et al.

Summary: The CCN family of matricellular proteins play essential roles in processes like angiogenesis, wound healing, and inflammation, particularly in the inflammatory pathologies of rheumatoid arthritis and osteoarthritis. Several proteins within the CCN family are thought to be potential therapeutic targets for these diseases.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Biochemistry & Molecular Biology

CCN2 Aggravates the Immediate Oxidative Stress-DNA Damage Response following Renal Ischemia-Reperfusion Injury

Floris A. Valentijn et al.

Summary: This study investigates the impact of CCN2 inhibition on oxidative stress and DNA damage following renal ischemia-reperfusion injury (IRI). The results suggest that targeting CCN2 may help mitigate AKI by reducing oxidative stress-induced DNA damage and subsequent DDR. CCN2 knockout mice showed reduced DNA damage, DDR, and oxidative stress levels, indicating the potential benefit of CCN2 inhibition in limiting post-IRI AKI.

ANTIOXIDANTS (2021)

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Review Cell Biology

The Emerging Roles of CCN3 Protein in Immune-Related Diseases

Linan Peng et al.

Summary: CCN proteins are a family of ECM-associated proteins that include CCN1-6, with CCN3 being a member known for its multiple biological functions in cell growth, migration, and differentiation processes. Recent studies have highlighted the crucial regulatory role of CCN3 in various immune-related diseases including rheumatology arthritis and osteoarthritis.

MEDIATORS OF INFLAMMATION (2021)

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Article Pharmacology & Pharmacy

CCN5 activation by free or encapsulated EGCG is required to render triple-negative breast cancer cell viability and tumor progression

Amlan Das et al.

Summary: This study demonstrates that EGCG activates CCN5 to inhibit in vitro cell viability, reverse TNBC cells' stemness, and suppress tumor growth. Additionally, EGCG-loaded nanoparticles are found to be more effective in suppressing tumors compared to free-EGCG.

PHARMACOLOGY RESEARCH & PERSPECTIVES (2021)

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Article Cardiac & Cardiovascular Systems

CCN family member 1 (CCN1) is an early marker of infarct size and left ventricular dysfunction in STEMI patients

Thabo Mahendiran et al.

Summary: CCN1 has been proposed as a novel biomarker for predicting short-term and long-term mortality in myocardial infarction patients, showing significant correlation with final infarct size and post-infarction left ventricular ejection fraction. Even in patients with normal classical cardiac biomarker levels, CCN1 remains a significant predictor and improves the discriminatory capacity of the CADILLAC score.

ATHEROSCLEROSIS (2021)

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Article Oncology

Matricellular Protein WISP2 Is an Endogenous Inhibitor of Collagen Linearization and Cancer Metastasis

Jagadeesh Janjanam et al.

Summary: This study identifies WISP2 as the first inhibitor of collagen linearization, which can normalize collagen architecture and inhibit metastasis by therapeutically restoring a high WISP2: WISP1 ratio.

CANCER RESEARCH (2021)

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Article Biochemistry & Molecular Biology

Resveratrol ameliorates the glucose uptake and lipid metabolism in gestational diabetes mellitus mice and insulin-resistant adipocytes via miR-23a-3p/NOV axis

Tao Zheng et al.

Summary: The study demonstrated that resveratrol improved glucose uptake and lipid metabolism of GDM mice and adipocytes with IR by regulating the miR-23a-3p/NOV axis.

MOLECULAR IMMUNOLOGY (2021)

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Article Oncology

Blood-based detection of lung cancer using cysteine-rich angiogenic inducer 61 (CYR61) as a circulating protein biomarker: a pilot study

Lucija Ackar et al.

Summary: Elevated CYR61 concentrations in plasma may improve the detection of lung cancer in men, but it is not effective in women due to low sensitivity and specificity.

MOLECULAR ONCOLOGY (2021)

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Review Cell Biology

Cellular communication network factor 3 in cartilage development and maintenance

Satoshi Kubota et al.

Summary: CCN3, a classical member of the CCN family, exhibits multiple functionalities with common molecular structures. In addition to its pathological associations with diseases, CCN3 plays important roles in the development and homeostasis of mammalian species, particularly in cartilage tissues.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2021)

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Review Cell Biology

CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology

Veronica Giusti et al.

Summary: The CCN family of proteins play crucial roles in cellular communication and have significant impacts on the development, physiology, inflammatory pathologies, and cancers affecting the musculoskeletal system. Their complex and multiple roles in various processes make them intriguing therapeutic targets.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2021)

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Review Cell Biology

Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine

Mangesh D. Hade et al.

Summary: Exosomes are extracellular vesicles secreted by almost all cell types to aid in various cellular functions, including intercellular communication and immune signaling. They carry a multitude of signaling moieties, making them potential candidates for tissue engineering and regenerative medicine. The review highlights the emerging roles and potential applications of exosomes in regenerative medicine, particularly in brain injuries, cardiovascular disease, and COVID-19.

CELLS (2021)

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Article Oncology

Potential Role of CCN Proteins in Breast Cancer: Therapeutic Advances and Perspectives

Kazi Ahsan Ahmed et al.

Summary: CCNs are a specific type of matricellular protein that play essential roles in various biological processes such as cell adhesion, angiogenesis, and tumorigenesis in vertebrates. Different members of the CCN family may have either favorable or unfavorable associations with breast cancer. Recent studies have revealed the dual nature of tumor inhibition and promotion for certain CCNs in breast cancer.

CURRENT ONCOLOGY (2021)

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Review Medicine, Research & Experimental

Tumor innervation: peripheral nerves take control of the tumor microenvironment

Stefan M. Gysler et al.

Summary: Recent cancer research has shifted focus from abnormal cell division to the complex interactions between cancer and noncancer cells in the tumor microenvironment. The recruitment of peripheral nerves to the TME by tumors has been linked to enhanced tumor growth and aggressive tumor behavior, suggesting a potential role for the peripheral nervous system in cancer development. Emerging evidence also suggests that exosomes may mediate neural regulation of the TME through cell-cell communication.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Review Oncology

Targeting CTGF in Cancer: An Emerging Therapeutic Opportunity

Yi-Wen Shen et al.

Summary: This article provides a comprehensive discussion on the role of connective tissue growth factor (CTGF) in cancer initiation, progression, and metastasis, as well as its importance in the tumor microenvironment. The authors suggest that CTGF is a promising cancer therapeutic target that could potentially improve clinical outcomes.

TRENDS IN CANCER (2021)

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Article Oncology

Nephroblastoma overexpressed protein (NOV) enhances 5-Fu-mediated inhibitory effect of colorectal cancer cell proliferation via JNK/AP-1/caspase-8/caspase-3 pathway

Dong Wang et al.

Summary: NOV can sensitize CRC cells towards 5-Fu-mediated inhibitory effect on cell proliferation through the JNK/AP-1/Caspase-8/Caspase-3 pathway.

DISCOVER ONCOLOGY (2021)

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Article Oncology

miR-26a-5p alleviates lipopolysaccharide-induced acute lung injury by targeting the connective tissue growth factor

Hongyan Li et al.

Summary: The study demonstrated that miR-26a-5p attenuated lung inflammation and apoptosis in LPS-induced ALI by targeting CTGF.

MOLECULAR MEDICINE REPORTS (2021)

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Article Cell & Tissue Engineering

Cell Communication Network Factor 4 (CCN4/WISP1) Shifts Melanoma Cells from a Fragile Proliferative State to a Resilient Metastatic State

Wentao Deng et al.

CELLULAR AND MOLECULAR BIOENGINEERING (2020)

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Article Cell Biology

Circulating Wnt1-inducible signaling pathway protein-1 (WISP-1/CCN4) is a novel biomarker of adiposity in subjects with type 2 diabetes

Vadim V. Klimontov et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2020)

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Article Clinical Neurology

Use of high-sensitivity digital ELISA improves the diagnostic performance of circulating brain-specific proteins for detection of traumatic brain injury during triage

Grant C. O'Connell et al.

NEUROLOGICAL RESEARCH (2020)

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Article Cardiac & Cardiovascular Systems

The senescence-associated matricellular protein CCN1 in plasma of human subjects with idiopathic pulmonary fibrosis

Tejaswini Kulkarni et al.

RESPIRATORY MEDICINE (2020)

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Article Multidisciplinary Sciences

CCN1 is an opsonin for bacterial clearance and a direct activator of Toll-like receptor signaling

Joon-Il Jun et al.

NATURE COMMUNICATIONS (2020)

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Article Multidisciplinary Sciences

CCN1 promotes hepatic steatosis and inflammation in non-alcoholic steatohepatitis

Linling Ju et al.

SCIENTIFIC REPORTS (2020)

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Review Clinical Neurology

Prospects and Perspectives for WISP1 (CCN4) in Diabetes Mellitus

Kenneth Maiese

CURRENT NEUROVASCULAR RESEARCH (2020)

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Article Biochemical Research Methods

The thrombospondin module 1 domain of the matricellular protein CCN3 shows an atypical disulfide pattern and incomplete CWR layers

Emma-Ruoqi Xu et al.

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY (2020)

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Article Orthopedics

Blocking CTGF/CCN2 reverses neural fibrosis and sensorimotor declines in a rat model of overuse-induced median mononeuropathy

Mary F. Barbe et al.

JOURNAL OF ORTHOPAEDIC RESEARCH (2020)

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Article Multidisciplinary Sciences

Quantitative proteomic landscape of metaplastic breast carcinoma pathological subtypes and their relationship to triple-negative tumors

Sabra Djomehri et al.

NATURE COMMUNICATIONS (2020)

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Editorial Material Cell Biology

Slow train coming: an anti-CCN2 strategy reverses a model of chronic overuse muscle fibrosis

Andrew Leask

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2020)

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Article Cell Biology

CCN-Based Therapeutic Peptides Modify Pancreatic Ductal Adenocarcinoma Microenvironment and Decrease Tumor Growth in Combination with Chemotherapy

Andrea Resovi et al.

CELLS (2020)

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Article Biochemistry & Molecular Biology

CCN6 regulates mitochondrial respiratory complex assembly and activity

Deepesh Kumar Padhan et al.

FASEB JOURNAL (2020)

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Article Oncology

Connective tissue growth factor produced by cancer-associated fibroblasts correlates with poor prognosis in epithelioid malignant pleural mesothelioma

Yuuki Ohara et al.

ONCOLOGY REPORTS (2020)

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Review Medicine, Research & Experimental

Regulation of cellular senescence by extracellular matrix during chronic fibrotic diseases

Kaj E. C. Blokland et al.

CLINICAL SCIENCE (2020)

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Review Biochemistry & Molecular Biology

The Roles of CCN1/CYR61 in Pulmonary Diseases

Yin Zhu et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Article Cell Biology

WISP1 alleviates lipid deposition in macrophages via the PPARγ/CD36 pathway in the plaque formation of atherosclerosis

Dian Liu et al.

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2020)

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Article Oncology

Gemcitabine/nab-paclitaxel with pamrevlumab: a novel drug combination and trial design for the treatment of locally advanced pancreatic cancer

Vincent Picozzi et al.

ESMO OPEN (2020)

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Review Cell Biology

Senescence and the SASP: many therapeutic avenues

Jodie Birch et al.

GENES & DEVELOPMENT (2020)

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Article Multidisciplinary Sciences

Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells

Rebeca Fernandez-Ruiz et al.

NATURE COMMUNICATIONS (2020)

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Article Cell Biology

Liver cancer: WISP3 suppresses hepatocellular carcinoma progression by negative regulation of β-catenin/TCF/LEF signalling

Hong Gao et al.

CELL PROLIFERATION (2019)

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Article Cell & Tissue Engineering

Aging Disrupts Muscle Stem Cell Function by Impairing Matricellular WISP1 Secretion from Fibro-Adipogenic Progenitors

Laura Lukjanenko et al.

CELL STEM CELL (2019)

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Letter Cardiac & Cardiovascular Systems

CCN1-Induced Cellular Senescence Promotes Heart Regeneration

Teng Feng et al.

CIRCULATION (2019)

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Article Biochemistry & Molecular Biology

The tumor cell-secreted matricellular protein WISP1 drives pro-metastatic collagen linearization

Hong Jia et al.

EMBO JOURNAL (2019)

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Article Biochemistry & Molecular Biology

CCN1-Yes-Associated Protein Feedback Loop Regulates Physiological and Pathological Angiogenesis

Sangmi Lee et al.

MOLECULAR AND CELLULAR BIOLOGY (2019)

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Article Cell Biology

Aging differentially modulates the Wnt pro-survival signalling pathways in vascular smooth muscle cells

Bethan A. Brown et al.

AGING CELL (2019)

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Article Cell Biology

A reproducible scaffold-free 3D organoid model to study neoplastic progression in breast cancer

Sabra I. Djomehri et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2019)

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Review Cell Biology

CCN5/WISP2 and metabolic diseases

John R. Grunberg et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2018)

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Article Cell Biology

Assessment of circulating Wnt1 inducible signalling pathway protein 1 (WISP-1)/CCN4 as a novel biomarker of obesity

Christopher Tacke et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2018)

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Article Oncology

Leptin-induced ER-α-positive breast cancer cell viability and migration is mediated by suppressing CCN5-signaling via activating JAK/AKT/STAT-pathway

Inamul Haque et al.

BMC CANCER (2018)

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Article Endocrinology & Metabolism

The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes

Tina Hoerbeit et al.

DIABETOLOGIA (2018)

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Article Cell Biology

WISP1 promotes non-alcoholic fatty liver disease and skeletal muscle insulin resistance via TLR4/JNK signaling

Tae Woo Jung et al.

JOURNAL OF CELLULAR PHYSIOLOGY (2018)

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Review Cell Biology

Matricellular CCN6 (WISP3) protein: a tumor suppressor for mammary metaplastic carcinomas

Mai N. Tran et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2018)

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Article Cell Biology

CCN5 in alveolar epithelial proliferation and differentiation during neonatal lung oxygen injury

Najla Fiaturi et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2018)

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Article Medicine, General & Internal

The correlation of Cyr61, CTGF, and VEGF with polymyositis/dermatomyositis

Ke-Xia Chai et al.

MEDICINE (2018)

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Review Oncology

The role of CCN4/WISP-1 in the cancerous phenotype

Mary P. Nivison et al.

CANCER MANAGEMENT AND RESEARCH (2018)

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Article Multidisciplinary Sciences

The matricellular protein CCN5 inhibits fibrotic deformation of retinal pigment epithelium

Aeri Yoon et al.

PLOS ONE (2018)

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Editorial Material Cell Biology

The official unified nomenclature adopted by the HGNC calls for the use of the acronyms, CCN1-6, and discontinuation in the use of CYR61, CTGF, NOV and WISP 1-3 respectively

Bernard Perbal et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2018)

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Article Medicine, Research & Experimental

Characterization of Wnt1-inducible Signaling Pathway Protein-1 in Obese Children and Adolescents

An-ru Wang et al.

CURRENT MEDICAL SCIENCE (2018)

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Article Cardiac & Cardiovascular Systems

miR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal Transition Therapeutic Implications in Kawasaki Disease

Ming He et al.

CIRCULATION RESEARCH (2017)

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Article Obstetrics & Gynecology

WISP1 is a novel adipokine linked to metabolic parameters in gestational diabetes mellitus

Gulcin Sahin Ersoy et al.

JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE (2017)

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Article Cell Biology

CCN2 induces cellular senescence in fibroblasts

Joon-Ii Jun et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2017)

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Article Biochemistry & Molecular Biology

Degradomic and yeast 2-hybrid inactive catalytic domain substrate trapping identifies new membrane-type 1 matrix metalloproteinase (MMP14) substrates: CCN3 (Nov) and CCN5 (WISP2)

Georgina S. Butler et al.

MATRIX BIOLOGY (2017)

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Article Multidisciplinary Sciences

WISP1/CCN4 inhibits adipocyte differentiation through repression of PPARγ activity

Nathalie Ferrand et al.

SCIENTIFIC REPORTS (2017)

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Article Oncology

CCN5/WISP-2 restores ER-α in normal and neoplastic breast cells and sensitizes triple negative breast cancer cells to tamoxifen

S. Sarkar et al.

ONCOGENESIS (2017)

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Article Multidisciplinary Sciences

Deficiency of CCN5/WISP-2-Driven Program in breast cancer Promotes Cancer Epithelial cells to mesenchymal stem cells and Breast Cancer growth

Amlan Das et al.

SCIENTIFIC REPORTS (2017)

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Article Endocrinology & Metabolism

WISP1 Is a Marker of Systemic and Adipose Tissue Inflammation in Dysmetabolic Subjects With or Without Type 2 Diabetes

Ilaria Barchetta et al.

JOURNAL OF THE ENDOCRINE SOCIETY (2017)

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Article Pathology

CCN3 Regulates Macrophage Foam Cell Formation and Atherosclerosis

Hong Shi et al.

AMERICAN JOURNAL OF PATHOLOGY (2017)

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Review Cell Biology

Regulation of the CCN genes by vitamin D: A possible adjuvant therapy in the treatment of cancer and fibrosis

Richard T. Piszczatowski et al.

CELLULAR SIGNALLING (2016)

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Article Oncology

The matricellular protein ccn6 (WISP3) decreases notch1 and suppresses breast cancer initiating cells

Wei Huang et al.

ONCOTARGET (2016)

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Review Cell Biology

Emerging roles of CCN proteins in vascular development and pathology

Philip A. Klenotic et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2016)

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Review Cell Biology

Human pancreatic cancer progression: an anarchy among CCN-siblings

Sushanta K. Banerjee et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2016)

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Review Cell Biology

The role of the CCN family of proteins in blood cancers

Lisa Judith Crawford et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2016)

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Review Cell Biology

Dual roles of CCN proteins in breast cancer progression

Celina G. Kleer

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2016)

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Article Medicine, Research & Experimental

CCN5 attenuates profibrotic phenotypes of fibroblasts through the Smad6-CCN2 pathway: Potential role in epidural fibrosis

Honghai Xu et al.

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE (2015)

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Review Medicine, Research & Experimental

Emerging role of CCN family proteins in tumorigenesis and cancer metastasis (Review)

Jun Li et al.

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE (2015)

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Article Biochemistry & Molecular Biology

CCN4 regulates vascular smooth muscle cell migration and proliferation

Hao Liu et al.

MOLECULES AND CELLS (2013)

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Article Multidisciplinary Sciences

Plasma NOV/CCN3 Levels Are Closely Associated with Obesity in Patients with Metabolic Disorders

Jihane Pakradouni et al.

PLOS ONE (2013)

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Article Multidisciplinary Sciences

WISP1/CCN4: A Potential Target for Inhibiting Prostate Cancer Growth and Spread to Bone

Mitsuaki Ono et al.

PLOS ONE (2013)

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Article Cell Biology

On how CCN6 suppresses breast cancer growth and invasion

Wei Huang et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2012)

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Article Cell Biology

CCN3 suppresses mitogenic signalling and reinstates growth control mechanisms in Chronic Myeloid Leukaemia

Lynn McCallum et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2012)

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Review Cell Biology

CCN5/WISP-2: A micromanager of breast cancer progression

Sushanta K. Banerjee et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2012)

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Review Biochemistry & Molecular Biology

The CCN family: A new class of inflammation modulators?

L. Kular et al.

BIOCHIMIE (2011)

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Review Biotechnology & Applied Microbiology

Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets

Joon-Il Jun et al.

NATURE REVIEWS DRUG DISCOVERY (2011)

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Article Cell Biology

Cellular senescence controls fibrosis in wound healing

Joon-Il Jun et al.

AGING-US (2010)

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Article Oncology

Differential expression of the CCN family member WISP-1, WISP-2 and WISP-3 in human colorectal cancer and the prognostic implications

Simon R. Davies et al.

INTERNATIONAL JOURNAL OF ONCOLOGY (2010)

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Article Cell Biology

The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing

Joon-Il Jun et al.

NATURE CELL BIOLOGY (2010)

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Editorial Material Cell Biology

Yin and Yang Part Deux: CCN5 inhibits the pro-fibrotic effects of CCN2

Andrew Leask

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2010)

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Review Cell Biology

CCN5: biology and pathophysiology

Joshua W. Russo et al.

JOURNAL OF CELL COMMUNICATION AND SIGNALING (2010)

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Review Hematology

CCN3-A key regulator of the hematopoietic compartment

L. McCallum et al.

BLOOD REVIEWS (2009)

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Article Pathology

Prognostic relevance of CCN3 in Ewing sarcoma

Bernard Perbal et al.

HUMAN PATHOLOGY (2009)

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Article Biochemistry & Molecular Biology

Role of WISP-2/CCN5 in the maintenance of a differentiated and noninvasive phenotype in human breast cancer cells

Asmaa Fritah et al.

MOLECULAR AND CELLULAR BIOLOGY (2008)

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Review Oncology

WISP3 and RhoC guanosine triphosphatase cooperate in the development of inflammatory breast cancer

CG Kleer et al.

BREAST CANCER RESEARCH (2004)

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Article Pathology

CCN5 is a growth arrest-specific gene that regulates smooth muscle cell proliferation and motility

AC Lake et al.

AMERICAN JOURNAL OF PATHOLOGY (2003)

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Article Endocrinology & Metabolism

Characterization of human NOV in biological fluids: An enzyme immunoassay for the quantification of human NOV in sera from patients with diseases of the adrenal gland and of the nervous system

H Thibout et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2003)

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