Alpha-Enolase (ENO1) Correlates with Invasiveness of Cutaneous Melanoma-An In Vitro and a Clinical Study

Overview

Journal Diagnostics (Basel)

Specialty Radiology

Date 2022 Feb 25

PMID 35204345

Authors

Miriam Hippner

Michal Majkowski

Przemyslaw Biecek

Teresa Szkudlarek

Aleksandra Simiczyjew

Malgorzata Pieniazek

Dorota Nowak

Arkadiusz Miazek

Piotr Donizy

Affiliations

Soon will be listed here.

Abstract

Alpha-enolase (ENO1) is a glycolytic metalloenzyme, and its overexpression occurs in numerous cancers, contributing to cancer cell survival, proliferation, and maintenance of the Warburg effect. Patients with an overexpression of ENO1 have a poor prognosis. The aim of the present study was to investigate the prognostic significance of ENO1 in surgical resections from 112 melanoma patients and to assess its expression and enzymatic activity in normoxia and hypoxia in several melanoma cell lines. Overexpression of ENO1 in tumor cells from patients was correlated with unfavorable prognosticators such as Breslow thickness, Clark level, mitotic activity, and the presence of ulceration. The expression of ENO1 also positively correlated with a greater thickness of the neoplastic infiltrate and a worse long-term prognosis for patients with cutaneous melanoma. We report significantly higher expression of ENO1 in melanoma cell lines in comparison to normal melanocytes. To conclude, our in vitro and clinical models showed that overexpression of ENO1 promotes invasiveness of melanoma cells and correlates with aggressive clinical behavior. These observations open the way to further search of a potential prognostic and therapeutic target in cutaneous melanoma.

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References

Li M, Li J, Wang J, Li Y, Yang P . Serum level of anti-α-enolase antibody in untreated systemic lupus erythematosus patients correlates with 24-hour urine protein and D-dimer. Lupus. 2017; 27(1):139-142. DOI: 10.1177/0961203317721752. View

Algazi A, Tsai K, Shoushtari A, Munhoz R, Eroglu Z, Piulats J . Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-L1 antibodies. Cancer. 2016; 122(21):3344-3353. PMC: 5767160. DOI: 10.1002/cncr.30258. View

Park H, Kim J, Sun B, Song S, Suh W, Sung J . Hypoxia induces glucose uptake and metabolism of adipose‑derived stem cells. Mol Med Rep. 2016; 14(5):4706-4714. DOI: 10.3892/mmr.2016.5796. View

Dratkiewicz E, Pietraszek-Gremplewicz K, Simiczyjew A, Mazur A, Nowak D . Gefitinib or lapatinib with foretinib synergistically induce a cytotoxic effect in melanoma cell lines. Oncotarget. 2018; 9(26):18254-18268. PMC: 5915070. DOI: 10.18632/oncotarget.24810. View

Capello M, Ferri-Borgogno S, Cappello P, Novelli F . α-Enolase: a promising therapeutic and diagnostic tumor target. FEBS J. 2011; 278(7):1064-74. DOI: 10.1111/j.1742-4658.2011.08025.x. View

Didiasova M, Schaefer L, Wygrecka M . When Place Matters: Shuttling of Enolase-1 Across Cellular Compartments. Front Cell Dev Biol. 2019; 7:61. PMC: 6498095. DOI: 10.3389/fcell.2019.00061. View

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T . Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012; 9(7):676-82. PMC: 3855844. DOI: 10.1038/nmeth.2019. View

Hu T, Liu H, Liang Z, Wang F, Zhou C, Zheng X . Tumor-intrinsic CD47 signal regulates glycolysis and promotes colorectal cancer cell growth and metastasis. Theranostics. 2020; 10(9):4056-4072. PMC: 7086360. DOI: 10.7150/thno.40860. View

Zhang T, Suo C, Zheng C, Zhang H . Hypoxia and Metabolism in Metastasis. Adv Exp Med Biol. 2019; 1136:87-95. DOI: 10.1007/978-3-030-12734-3_6. View

10.

Wang L, Bi R, Yin H, Liu H, Li L . ENO1 silencing impaires hypoxia-induced gemcitabine chemoresistance associated with redox modulation in pancreatic cancer cells. Am J Transl Res. 2019; 11(7):4470-4480. PMC: 6684912. View

11.

Cho H, Um J, Lee J, Kim W, Kang W, Kim S . ENOblock, a unique small molecule inhibitor of the non-glycolytic functions of enolase, alleviates the symptoms of type 2 diabetes. Sci Rep. 2017; 7:44186. PMC: 5341156. DOI: 10.1038/srep44186. View

12.

Conforti C, Zalaudek I . Epidemiology and Risk Factors of Melanoma: A Review. Dermatol Pract Concept. 2021; 11(Suppl 1):e2021161S. PMC: 8366310. DOI: 10.5826/dpc.11S1a161S. View

13.

Simiczyjew A, Pietraszek-Gremplewicz K, Dratkiewicz E, PodgOrska M, Matkowski R, Zietek M . Combination of Selected MET and EGFR Inhibitors Decreases Melanoma Cells' Invasive Abilities. Front Pharmacol. 2019; 10:1116. PMC: 6792435. DOI: 10.3389/fphar.2019.01116. View

14.

Chang Y, Wu W, Walsh G, Hong W, Mao L . Enolase-alpha is frequently down-regulated in non-small cell lung cancer and predicts aggressive biological behavior. Clin Cancer Res. 2003; 9(10 Pt 1):3641-4. View

15.

Liu Z, Zhang A, Zheng L, Johnathan A, Zhang J, Zhang G . The Biological Significance and Regulatory Mechanism of c-Myc Binding Protein 1 (MBP-1). Int J Mol Sci. 2018; 19(12). PMC: 6320933. DOI: 10.3390/ijms19123868. View

16.

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

17.

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

18.

Rastrelli M, Tropea S, Rossi C, Alaibac M . Melanoma: epidemiology, risk factors, pathogenesis, diagnosis and classification. In Vivo. 2014; 28(6):1005-11. View

19.

Donizy P, Wu C, Mull J, Fujimoto M, Chlopik A, Peng Y . Up-Regulation of PARP1 Expression Significantly Correlated with Poor Survival in Mucosal Melanomas. Cells. 2020; 9(5). PMC: 7290913. DOI: 10.3390/cells9051135. View

20.

Rofstad E, Rasmussen H, Galappathi K, Mathiesen B, Nilsen K, Graff B . Hypoxia promotes lymph node metastasis in human melanoma xenografts by up-regulating the urokinase-type plasminogen activator receptor. Cancer Res. 2002; 62(6):1847-53. View