ENO1 and Cancer

Overview

Journal Mol Ther Oncolytics

Publisher Cell Press

Date 2022 Apr 18

PMID 35434271

Authors

Chen Kai Huang

Ying Sun

Lei Lv

Yong Ping

Affiliations

Soon will be listed here.

Abstract

α-Enolase (ENO1), also known as 2-phospho-D-glycerate hydrolase, is a glycolytic enzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid during glycolysis. It is a multifunctional oncoprotein that is present both in cell surface and cytoplasm, contributing to hit seven out of ten "hallmarks of cancer." ENO1's glycolytic function deregulates cellular energetic, sustains tumor proliferation, and inhibits cancer cell apoptosis. Moreover, ENO1 evades growth suppressors and helps tumors to avoid immune destruction. Besides, ENO1 "moonlights" on the cell surface and acts as a plasminogen receptor, promoting cancer invasion and metastasis by inducing angiogenesis. Overexpression of ENO1 on a myriad of cancer types together with its localization on the tumor surface makes it a great prognostic and diagnostic cancer biomarker as well as an accessible oncotherapeutic target. This review summarizes the up-to-date knowledge about the relationship between ENO1 and cancer, examines ENO1's potential as a cancer biomarker, and discusses ENO1's role in novel onco-immunotherapeutic strategies.

Citing Articles

Natural product mediated mesenchymal-epithelial remodeling by covalently binding ENO1 to degrade m6A modified -catenin mRNA.

Chen T, Liu G, Chen S, Zhang F, Ma S, Bai Y Acta Pharm Sin B. 2025; 15(1):467-483.

PMID: 40041899 PMC: 11873566. DOI: 10.1016/j.apsb.2024.07.013.

Integrative machine learning model of RNA modifications predict prognosis and treatment response in patients with breast cancer.

Wang T, Wang S, Li Z, Xie J, Jia Q, Hou J Cancer Cell Int. 2025; 25(1):43.

PMID: 39948551 PMC: 11827143. DOI: 10.1186/s12935-025-03651-y.

Role of NAT10-mediated acC acetylation of ENO1 mRNA in glycolysis and apoptosis in non-small cell lung cancer cells.

Yuan Y, Li N, Zhu J, Shao C, Zeng X, Yi D BMC Pulm Med. 2025; 25(1):75.

PMID: 39948547 PMC: 11827380. DOI: 10.1186/s12890-024-03463-2.

Exploring RNA cargo in extracellular vesicles for pleural mesothelioma detection.

Kraft A, Kirschner M, Orlowski V, Ronner M, Bodmer C, Boeva V BMC Cancer. 2025; 25(1):212.

PMID: 39920655 PMC: 11804012. DOI: 10.1186/s12885-025-13617-y.

Multimodal lung cancer theranostics via manganese phosphate/quercetin particle.

Qiu C, Xia F, Tu Q, Tang H, Liu Y, Liu H Mol Cancer. 2025; 24(1):43.

PMID: 39905491 PMC: 11796208. DOI: 10.1186/s12943-025-02242-9.

References

Gemta L, Siska P, Nelson M, Gao X, Liu X, Locasale J . Impaired enolase 1 glycolytic activity restrains effector functions of tumor-infiltrating CD8 T cells. Sci Immunol. 2019; 4(31). PMC: 6824424. DOI: 10.1126/sciimmunol.aap9520. View

Zakrzewicz D, Didiasova M, Kruger M, Giaimo B, Borggrefe T, Mieth M . Protein arginine methyltransferase 5 mediates enolase-1 cell surface trafficking in human lung adenocarcinoma cells. Biochim Biophys Acta Mol Basis Dis. 2018; 1864(5 Pt A):1816-1827. DOI: 10.1016/j.bbadis.2018.02.021. View

Sun L, Lu T, Tian K, Zhou D, Yuan J, Wang X . Alpha-enolase promotes gastric cancer cell proliferation and metastasis via regulating AKT signaling pathway. Eur J Pharmacol. 2018; 845:8-15. DOI: 10.1016/j.ejphar.2018.12.035. View

Gao J, Zhao R, Xue Y, Niu Z, Cui K, Yu F . Role of enolase-1 in response to hypoxia in breast cancer: exploring the mechanisms of action. Oncol Rep. 2013; 29(4):1322-32. DOI: 10.3892/or.2013.2269. View

Zhou J, Zhang S, Chen Z, He Z, Xu Y, Li Z . CircRNA-ENO1 promoted glycolysis and tumor progression in lung adenocarcinoma through upregulating its host gene ENO1. Cell Death Dis. 2019; 10(12):885. PMC: 6877563. DOI: 10.1038/s41419-019-2127-7. View

Capello M, Ferri-Borgogno S, Riganti C, Chattaragada M, Principe M, Roux C . Targeting the Warburg effect in cancer cells through ENO1 knockdown rescues oxidative phosphorylation and induces growth arrest. Oncotarget. 2016; 7(5):5598-612. PMC: 4868708. DOI: 10.18632/oncotarget.6798. View

Liu Y, Li H, Liu Y, Zhu Z . MiR-22-3p targeting alpha-enolase 1 regulates the proliferation of retinoblastoma cells. Biomed Pharmacother. 2018; 105:805-812. DOI: 10.1016/j.biopha.2018.06.038. View

Hsiao K, Shih N, Fang H, Huang T, Kuo C, Chu P . Surface α-enolase promotes extracellular matrix degradation and tumor metastasis and represents a new therapeutic target. PLoS One. 2013; 8(7):e69354. PMC: 3716638. DOI: 10.1371/journal.pone.0069354. View

Fu Q, Liu Y, Fan Y, Hua S, Qu H, Dong S . Alpha-enolase promotes cell glycolysis, growth, migration, and invasion in non-small cell lung cancer through FAK-mediated PI3K/AKT pathway. J Hematol Oncol. 2015; 8:22. PMC: 4359783. DOI: 10.1186/s13045-015-0117-5. View

10.

De Rosa V, Galgani M, Porcellini A, Colamatteo A, Santopaolo M, Zuchegna C . Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants. Nat Immunol. 2015; 16(11):1174-84. PMC: 4868085. DOI: 10.1038/ni.3269. View

11.

Principe M, Borgoni S, Cascione M, Chattaragada M, Ferri-Borgogno S, Capello M . Alpha-enolase (ENO1) controls alpha v/beta 3 integrin expression and regulates pancreatic cancer adhesion, invasion, and metastasis. J Hematol Oncol. 2017; 10(1):16. PMC: 5237223. DOI: 10.1186/s13045-016-0385-8. View

12.

Ji H, Wang J, Guo J, Li Y, Lian S, Guo W . Progress in the biological function of alpha-enolase. Anim Nutr. 2018; 2(1):12-17. PMC: 5941012. DOI: 10.1016/j.aninu.2016.02.005. View

13.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

14.

Osthus R, Shim H, Kim S, Li Q, Reddy R, Mukherjee M . Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem. 2000; 275(29):21797-800. DOI: 10.1074/jbc.C000023200. View

15.

Sedoris K, Thomas S, Miller D . Hypoxia induces differential translation of enolase/MBP-1. BMC Cancer. 2010; 10:157. PMC: 2873388. DOI: 10.1186/1471-2407-10-157. View

16.

Shih N, Lai H, Chang G, Lin H, Wu Y, Liu J . Anti-alpha-enolase autoantibodies are down-regulated in advanced cancer patients. Jpn J Clin Oncol. 2010; 40(7):663-9. DOI: 10.1093/jjco/hyq028. View

17.

Zhang Y, Weinberg R . Epithelial-to-mesenchymal transition in cancer: complexity and opportunities. Front Med. 2018; 12(4):361-373. PMC: 6186394. DOI: 10.1007/s11684-018-0656-6. View

18.

Chen Q, Liu L, Lu Y, Chen X, Zhang Y, Zhou W . Tumor Microenvironment-Triggered Aggregated Magnetic Nanoparticles for Reinforced Image-Guided Immunogenic Chemotherapy. Adv Sci (Weinh). 2019; 6(6):1802134. PMC: 6425432. DOI: 10.1002/advs.201802134. View

19.

Lunt S, Vander Heiden M . Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol. 2011; 27:441-64. DOI: 10.1146/annurev-cellbio-092910-154237. View

20.

Gomez-Valenzuela F, Escobar E, Perez-Tomas R, Montecinos V . The Inflammatory Profile of the Tumor Microenvironment, Orchestrated by Cyclooxygenase-2, Promotes Epithelial-Mesenchymal Transition. Front Oncol. 2021; 11:686792. PMC: 8222670. DOI: 10.3389/fonc.2021.686792. View