Enolase 1 Regulates Stem Cell-Like Properties in Gastric Cancer Cells by Stimulating Glycolysis

Yang, Tao; Xiong, Shunbin; Zhang, Huiwen; Sun, Lixin; Liu, Yu; Li, Jun; Sun, Lichao; Yang, Zhihua; Ran, Yuliang

doi:10.21203/rs.3.rs-40874/v1

Cited by 11 publications

(13 citation statements)

References 27 publications

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“…Moreover, PGK1 is a kinase involved in oncogenic signaling, thus understanding the processes driven by DNA-PK/PGK1 interaction may identify novel mechanisms that drive proliferation and metastasis. Lastly, ENO1 is a glycolytic enzyme that has been shown to contribute to proliferation, metastasis and therapy resistance through its role in glycolysis [45]. ENO1 is overexpressed and promotes tumor growth in head and neck, hepatocellular and gastric cancers [45].…”

Section: Combination Of Dna-pk and Glycolysis Inhibitor Decreases Proliferation In Crpcmentioning

confidence: 99%

“…Lastly, ENO1 is a glycolytic enzyme that has been shown to contribute to proliferation, metastasis and therapy resistance through its role in glycolysis [45]. ENO1 is overexpressed and promotes tumor growth in head and neck, hepatocellular and gastric cancers [45]. Further interrogation of the DNA-PK/ENO1 interaction could expand our understanding of the role of DNA-PK in glycolysis and how these proteins together may impact response to therapy.…”

Section: Combination Of Dna-pk and Glycolysis Inhibitor Decreases Proliferation In Crpcmentioning

confidence: 99%

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A Novel Role for DNA-PK in Metabolism by Regulating Glycolysis in Castration-Resistant Prostate Cancer

Dylgjeri

Kothari

Shafi

et al. 2022

Clinical Cancer Research

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Purpose: DNA-dependent kinase catalytic subunit (DNA-PKcs, herein referred as DNA-PK) is a multifunctional kinase of high cancer relevance. DNA-PK is deregulated in multiple tumor types, including prostate cancer (PCa), and is associated with poor outcomes. DNA-PK was previously nominated as a therapeutic target and DNA-PK inhibitors are currently undergoing clinical investigation. While DNA-PK is well studied in DNA repair and transcriptional regulation, much remains to be understood about the way by which DNA-PK drives aggressive disease phenotypes.Experimental Design: Here, unbiased proteomic and metabolomic approaches in clinically relevant tumor models uncovered a novel role of DNA-PK in metabolic regulation of cancer progression. DNA-PK regulation of metabolism was interrogated using pharmacological and genetic perturbation using in vitro cell models, in vivo xenografts, and ex vivo in patient-derived explants (PDE).Results: Key findings reveal: i) the first-in-field DNA-PK protein-protein interactome; ii) numerous DNA-PK novel partners involved in glycolysis, iii) DNA-PK interacts with, phosphorylates (in vitro) and increases the enzymatic activity of glycolytic enzymes ALDOA and PKM2, iv) DNA-PK drives synthesis of glucose-derived pyruvate and lactate, v) DNA-PK regulates glycolysis in vitro, in vivo and ex vivo, and vi) combination of DNA-PK inhibitor with glycolytic inhibitor 2-deoxyglucose leads to additive antiproliferative effects in aggressive disease.Conclusions: Findings herein unveil novel DNA-PK partners, substrates, and function in PCa. The role of DNA-PK impacts glycolysis through direct interaction with glycolytic enzymes and modulation of enzymatic activity. These events support energy production Research.

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Section: Combination Of Dna-pk and Glycolysis Inhibitor Decreases Proliferation In Crpcmentioning

confidence: 99%

Section: Combination Of Dna-pk and Glycolysis Inhibitor Decreases Proliferation In Crpcmentioning

confidence: 99%

A Novel Role for DNA-PK in Metabolism by Regulating Glycolysis in Castration-Resistant Prostate Cancer

Dylgjeri

Kothari

Shafi

et al. 2022

Clinical Cancer Research

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“…Over the years, several ENO1 inhibitors have performed promising results of the pharmacological-based study and preclinical trials (20,21). As the non-enzymatic active site inhibitor of ENO1, ENOblock reflects cytotoxicity in hypoxic and normal conditions on colon cancer cells (22). In addition, a series of enzymatic active inhibitors of ENO1, such as phosphonoacetohydroxamate acid (PhAH), (1,5-dihydroxy-2-oxopyrrolidin-3-yl)phosphonic acid (SF2312), deoxy-SF2312, Methyl-SF2312, POMSF, POMHEX and its derivatives, show potential anticancer in the functional cancer models (21,23).…”

Section: Ivyspring International Publishermentioning

confidence: 99%

Enolase 1, a Moonlighting Protein, as a Potential Target for Cancer Treatment

Qiao¹,

Wu²,

Chen³

et al. 2021

Int. J. Biol. Sci.

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Enolase 1 (ENO1) is a moonlighting protein, function as a glycolysis enzyme, a plasminogen receptor and a DNA binding protein. ENO1 play an important role in the process of cancer development. The transcription, translation, post-translational modifying activities and the immunoregulatory role of ENO1 at the cancer development is receiving increasing attention. Some function model studies have shown that ENO1 is a potential target for cancer treatment. In this review, we provide a comprehensive overview of the characterization, function, related transduction cascades of ENO1 and its roles in the pathophysiology of cancers, which is a consequence of ENO1 signaling dysregulation. And the development of novels anticancer agents that targets ENO1 may provide a more attractive option for the treatment of cancers. The data of sarcoma and functional cancer models indicates that ENO1 may become a new potential target for anticancer therapy.

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“…As a glycolytic enzyme, ENO1 contributes to the Warburg effect and provides ATP to promote cancer development and progression [45]. In addition, ENO1 promotes the plasminogen activation system and upregulates integrin to enhance the migration and invasion of cancers [46][47][48]; ENO1 regulates gastric cancer cells stemness by stimulating glycolysis [49]. Our previous studies found that ENO1 promoted tumor proliferation, migration, and invasion in non-small cell lung cancer [50].…”

Section: Discussionmentioning

confidence: 99%

CCDC65, a Gene Knockout that leads to Early Death of Mice, acts as a potentially Novel Tumor Suppressor in Lung Adenocarcinoma

Zhang¹,

Xu²,

Hu³

et al. 2022

Int. J. Biol. Sci.

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CCDC65 is a member of the coiled-coil domain-containing protein family and was only reported in gastric cancer by our group. We first observed that it is downregulated in lung adenocarcinoma based on the TCGA database. Reduced CCDC65 protein was shown as an unfavorable factor promoting the clinical progression in lung adenocarcinoma. Subsequently, CCDC65 -/-mice were found possibly dead of hydrocephalus. Compared with the CCDC65 +/+ mice, the downregulation of CCDC65 in CCDC65 +/mice significantly increased the formation ability of lung cancer induced by urethane. In the subsequent investigation, we observed that CCDC65 functions as a tumor suppressor repressing cell proliferation in vitro and in vivo. Molecular mechanism showed that CCDC65 recruited E3 ubiquitin ligase FBXW7 to induce the ubiquitination degradation of c-Myc, an oncogenic transcription factor in tumors, and reduced c-Myc binding to ENO1 promoter, which suppressed the transcription of ENO1. In addition, CCDC65 also recruited FBXW7 to degrade ENO1 protein by ubiquitinated modulation. The downregulated ENO1 further reduced the phosphorylation activation of AKT1, which thus inactivated the cell cycle signal. Our data demonstrated that CCDC65 is a potential tumor suppressor by recruiting FBWX7 to suppress c-Myc/ENO1-induced cell cycle signal in lung adenocarcinoma.

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Enolase 1 Regulates Stem Cell-Like Properties in Gastric Cancer Cells by Stimulating Glycolysis

Cited by 11 publications

References 27 publications

A Novel Role for DNA-PK in Metabolism by Regulating Glycolysis in Castration-Resistant Prostate Cancer

A Novel Role for DNA-PK in Metabolism by Regulating Glycolysis in Castration-Resistant Prostate Cancer

Enolase 1, a Moonlighting Protein, as a Potential Target for Cancer Treatment

CCDC65, a Gene Knockout that leads to Early Death of Mice, acts as a potentially Novel Tumor Suppressor in Lung Adenocarcinoma

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