Mediation of PKM2-dependent glycolytic and non-glycolytic pathways by ENO2 in head and neck cancer development

Article Biochemistry & Molecular Biology

PKM2 Modulation in Head and Neck Squamous Cell Carcinoma

Verena Boschert et al.

Summary: PKM2 is commonly phosphorylated at Tyr105 in HNSCC, and its levels depend on tyrosine kinase activity. It is also correlated with the expression of CD44 and has an impact on the metabolism of HNSCC cells.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Oncology

ATAD3A mediates activation of RAS-independent mitochondrial ERK1/2 signaling, favoring head and neck cancer development

Liwei Lang et al.

Summary: Targeting mitochondrial oncoproteins presents a new concept for effective cancer therapeutics. In this study, the researchers focused on ATAD3A and its impact on head and neck squamous cell carcinoma (HNSCC). They found that ATAD3A is highly expressed in HNSCC tissues and cell lines, and loss of ATAD3A expression suppresses HNSCC cell growth and leads to tumor regression. Mechanistically, they discovered that ATAD3A interacts with ERK1/2 in the mitochondria of HNSCC cells and this interaction is essential for the activation of mitochondrial ERK1/2 signaling. Most importantly, they showed that targeting ATAD3A in combination with RAS inhibitor treatment has a more significant tumor suppression effect. These findings highlight the potential of ATAD3A and RAS signaling as targets for HNSCC therapeutics.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2022)

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Article Oncology

NEDD4L inhibits glycolysis and proliferation of cancer cells in oral squamous cell carcinoma by inducing ENO1 ubiquitination and degradation

Guangping Zhang et al.

Summary: Glycolysis contributes to the cell metabolism and proliferation of oral squamous cell carcinoma (OSCC), the most common type of oral cancer. Understanding the regulatory mechanisms involved in glycolysis of OSCC cells may have important therapeutic implications. The study showed that NEDD4L is downregulated in OSCC tissues and its expression is positively correlated with 5-year patient survival rate. Overexpression of NEDD4L inhibited the proliferation, cell cycle transition, and glycolysis of OSCC cells, and suppressed tumor growth in vivo. ENO1, an enzyme involved in glycolysis, was identified as a substrate of NEDD4L. Overexpression of NEDD4L led to the ubiquitination and degradation of ENO1. The functional effects of NEDD4L overexpression were reversed by overexpression of ENO1. These findings reveal a signaling axis that is important for OSCC cell survival and metabolism and could serve as a potential therapeutic target.

CANCER BIOLOGY & THERAPY (2022)

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Article Oncology

The Quest to Eradicate HPV-Related Oropharyngeal Carcinoma: An Opportunity Not to Miss

Chloe S. Lalonde et al.

Summary: This article provides an overview of the necessary elements to eliminate oropharyngeal squamous cell carcinoma, including improved vaccine uptake, universal vaccination effort, and implementation of novel therapeutics to cure existing disease.

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE (2022)

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Review Oncology

ENO1 and Cancer

Chen Kai Huang et al.

Summary: This passage introduces the role of alpha-Enolase (ENO1) as a glycolytic enzyme in cancer. Additionally, it acts as a plasminogen receptor on the cell surface, promoting cancer invasion and metastasis. The overexpression of ENO1 and its localization on the tumor surface make it a prognostic and diagnostic cancer biomarker as well as a therapeutic target.

MOLECULAR THERAPY-ONCOLYTICS (2022)

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Article Oncology

A Novel Enolase-1 Antibody Targets Multiple Interacting Players in the Tumor Microenvironment of Advanced Prostate Cancer

Mao-Lin Chen et al.

Summary: This study found that targeting surface enolase-1 (ENO1) can inhibit the growth and metastasis of prostate cancer. In vivo experiments demonstrated that monoclonal antibodies against ENO1 can reduce tumor growth, angiogenesis, and activation of osteoclasts in the bone. Laboratory research also showed that the antibodies can block tube formation of endothelial cells and inhibit inflammation-induced cell migration.

MOLECULAR CANCER THERAPEUTICS (2022)

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Article Oncology

ENO1 suppresses cancer cell ferroptosis by degrading the mRNA of iron regulatory protein 1

Tong Zhang et al.

Summary: This study demonstrates the role of the glycolytic enzyme alpha-Enolase 1 in iron homeostasis and suppression of ferroptosis in hepatocellular carcinoma. The researchers found that ENO1 suppresses IRP1 expression to regulate iron balance in HCC cells, suggesting a potential innovative cancer therapy targeting the ENO1-IRP1-Mfrn1 pathway.

NATURE CANCER (2022)

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Article Immunology

Activator-Mediated Pyruvate Kinase M2 Activation Contributes to Endotoxin Tolerance by Promoting Mitochondrial Biogenesis

Zhujun Yi et al.

Summary: The PKM2 small-molecule agonist TEPP-46 activates PKM2 by inducing the formation of PKM2 tetramer and promotes macrophage endotoxin tolerance. TEPP-46-induced mitochondrial biogenesis in macrophages plays a key role in mediating endotoxin tolerance. Targeting PKM2 may provide a new therapeutic option for sepsis and inflammatory diseases.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Oncology

Blockade of glutamine-dependent cell survival augments antitumor efficacy of CPI-613 in head and neck cancer

Liwei Lang et al.

Summary: The study reveals that head and neck squamous cell carcinoma cells are highly dependent on glutamine, and a novel lipoate analog, CPI-613, redirects cellular metabolism towards tumor-promoting glutaminolysis, reducing the efficacy of anticancer drugs in HNSCC cells. Combining a GLS1 inhibitor, CB-839, with CPI-613 can overcome metabolic dependency on glutamine and achieve a synergistic anticancer effect in glutamine-addicted HNSCC.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2021)

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Review Oncology

The Hidden Link of Exosomes to Head and Neck Cancer

Yong Teng et al.

Summary: Head and neck squamous cell carcinomas (HNSCC) present a challenging group of malignancies that require a multidisciplinary management approach, with limited advancements in targeted therapeutics. Recent progress in immunotherapeutic approaches has shown positive effects on clinical outcomes for patients with advanced disease, highlighting the urgent need for novel systemic therapies for this type of cancer. The role of exosomes in sustaining malignant cells in HNSCC and the potential for future therapeutic interventions based on current evidence are areas of increasing interest.

CANCERS (2021)

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Review Medicine, General & Internal

Head and neck cancer

Mayur D. Mody et al.

Summary: Head and neck cancer is the seventh most common type of cancer worldwide, with the predominant risk factors being tobacco use, alcohol abuse, and oncogenic viruses. Treatment typically involves a multidisciplinary approach with surgery, radiotherapy, and systemic therapy, and is challenging due to site-specific and histology-specific variations.

LANCET (2021)

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Article Biochemistry & Molecular Biology

Specific Pyruvate Kinase M2 Inhibitor, Compound 3K, Induces Autophagic Cell Death through Disruption of the Glycolysis Pathway in Ovarian Cancer Cells

Jae Hyeon Park et al.

Summary: The study demonstrated that compound 3K had anticancer effects on PKM2-overexpressing ovarian cancer cells by regulating autophagic and apoptotic pathways, inhibiting tumor progression and reducing cell proliferation. Inhibition of PKM2 by compound 3K affected the Warburg effect and induced autophagic cell death, offering a promising therapeutic approach for treating PKM2-overexpressing ovarian cancer.

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES (2021)

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Review Oncology

Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis

Kulsoom Zahra et al.

FRONTIERS IN ONCOLOGY (2020)

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Review Biochemistry & Molecular Biology

Targeting Hypoxia-Driven Metabolic Reprogramming to Constrain Tumor Progression and Metastasis

Marisol Miranda-Galvis et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Review Endocrinology & Metabolism

Metabolic landscape of oral squamous cell carcinoma

Jessica Gardone Vitorio et al.

METABOLOMICS (2020)

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Article Cell Biology

Enolase 1 regulates stem cell-like properties in gastric cancer cells by stimulating glycolysis

Ting Yang et al.

CELL DEATH & DISEASE (2020)

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Article Medicine, General & Internal

Head and neck squamous cell carcinoma

Daniel E. Johnson et al.

NATURE REVIEWS DISEASE PRIMERS (2020)

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Article Endocrinology & Metabolism

An enolase inhibitor for the targeted treatment of ENO1-deleted cancers

Yu-Hsi Lin et al.

NATURE METABOLISM (2020)

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Article Biochemistry & Molecular Biology

Insulin-like growth factor 1-induced enolase 2 deacetylation by HDAC3 promotes metastasis of pancreatic cancer

Yan Zheng et al.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2020)

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Article Cell Biology

Intracellular citrate accumulation by oxidized ATM-mediated metabolism reprogramming via PFKP and CS enhances hypoxic breast cancer cell invasion and metastasis

Meixi Peng et al.

CELL DEATH & DISEASE (2019)

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Article Biochemistry & Molecular Biology

FGF19 amplification reveals an oncogenic dependency upon autocrine FGF19/FGFR4 signaling in head and neck squamous cell carcinoma

Lixia Gao et al.

ONCOGENE (2019)

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Article Cell Biology

ENO2 Promotes Cell Proliferation, Glycolysis, and Glucocorticoid-Resistance in Acute Lymphoblastic Leukemia

Cheng-cheng Liu et al.

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY (2018)

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Article Genetics & Heredity

Autophagy blockade sensitizes human head and neck squamous cell carcinoma towards CYT997 through enhancing excessively high reactive oxygen species-induced apoptosis

Lixia Gao et al.

JOURNAL OF MOLECULAR MEDICINE-JMM (2018)

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Review Biochemistry & Molecular Biology

Pyruvate kinase M2 fuels multiple aspects of cancer cells: from cellular metabolism, transcriptional regulation to extracellular signaling

Ming-Chuan Hsu et al.

MOLECULAR CANCER (2018)

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Article Biochemistry & Molecular Biology

Targeting the Warburg effect via LDHA inhibition engages ATF4 signaling for cancer cell survival

Gaurav Pathria et al.

EMBO JOURNAL (2018)

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Article Biochemistry & Molecular Biology

FGFR4 provides the conduit to facilitate FGF19 signaling in breast cancer progression

Xiangdong Zhao et al.

MOLECULAR CARCINOGENESIS (2018)

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Article Multidisciplinary Sciences

ENOblock, a unique small molecule inhibitor of the non-glycolytic functions of enolase, alleviates the symptoms of type 2 diabetes

Haaglim Cho et al.

SCIENTIFIC REPORTS (2017)

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Review Cell Biology

The Emerging Hallmarks of Cancer Metabolism

Natalya N. Pavlova et al.

CELL METABOLISM (2016)

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Review Biochemistry & Molecular Biology

PKM2, cancer metabolism, and the road ahead

Talya L. Dayton et al.

EMBO REPORTS (2016)

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Article Oncology

Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial

Tanguy Y. Seiwert et al.

LANCET ONCOLOGY (2016)

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Article Medicine, General & Internal

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck

R. L. Ferris et al.

NEW ENGLAND JOURNAL OF MEDICINE (2016)

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Review Biochemistry & Molecular Biology

The Warburg Effect: How Does it Benefit Cancer Cells?

Maria V. Liberti et al.

TRENDS IN BIOCHEMICAL SCIENCES (2016)

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Article Oncology

PKM2 and cancer: The function of PKM2 beyond glycolysis

Gaochao Dong et al.

ONCOLOGY LETTERS (2016)

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Article Multidisciplinary Sciences

ENOblock Does Not Inhibit the Activity of the Glycolytic Enzyme Enolase

Nikunj Satani et al.

PLOS ONE (2016)

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Article Cell Biology

IGF1 regulates PKM2 function through Akt phosphorylation

Barbara Salani et al.

CELL CYCLE (2015)

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Article Medicine, General & Internal

The Correlations Between MRI Perfusion, Diffusion Parameters, and 18F-FDG PET Metabolic Parameters in Primary Head-and-Neck Cancer A Cross-Sectional Analysis in Single Institute

Miran Han et al.

MEDICINE (2015)

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Review Cell Biology

Pyruvate kinase: Function, regulation and role in cancer

William J. Israelsen et al.

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY (2015)

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Article Oncology

PKM2 promotes glucose metabolism and cell growth in gliomas through a mechanism involving a let-7a/c-Myc/hnRNPA1 feedback loop

Wenkang Luan et al.

ONCOTARGET (2015)

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Article Oncology

High glucose uptake unexpectedly is accompanied by high levels of the mitochondrial β-F1-ATPase subunit in head and neck squamous cell carcinoma

Christian U. Huebbers et al.

ONCOTARGET (2015)

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Article Biochemistry & Molecular Biology

A Unique Small Molecule Inhibitor of Enolase Clarifies Its Role in Fundamental Biological Processes

Da-Woon Jung et al.

ACS CHEMICAL BIOLOGY (2013)

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Article Biochemistry & Molecular Biology

PKM2 Phosphorylates Histone H3 and Promotes Gene Transcription and Tumorigenesis

Weiwei Yang et al.

CELL (2012)

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Review Otorhinolaryngology

Altered metabolism in head and neck squamous cell carcinoma: an opportunity for identification of novel biomarkers and drug targets

Vlad C. Sandulache et al.

HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK (2012)

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Article Cell Biology

ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect

Weiwei Yang et al.

NATURE CELL BIOLOGY (2012)

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Article Biochemistry & Molecular Biology

Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis

Dimitrios Anastasiou et al.

NATURE CHEMICAL BIOLOGY (2012)

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Article Multidisciplinary Sciences

Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation

Weiwei Yang et al.

NATURE (2011)

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Article Biochemistry & Molecular Biology

Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2

J. Chen et al.

ONCOGENE (2011)

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Article Biochemistry & Molecular Biology

EGF-Induced ERK Activation Promotes CK2-Mediated Disassociation of α-Catenin from β-Catenin and Transactivation of β-Catenin

Haitao Ji et al.

MOLECULAR CELL (2009)

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Article Multidisciplinary Sciences

Pyruvate kinase M2 is a phosphotyrosine-binding protein

Heather R. Christofk et al.

NATURE (2008)

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Article Multidisciplinary Sciences

The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth

Heather R. Christofk et al.

NATURE (2008)

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Review Biochemistry & Molecular Biology

The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention

John P. Alao

MOLECULAR CANCER (2007)

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Mediation of PKM2-dependent glycolytic and non-glycolytic pathways by ENO2 in head and neck cancer development

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