Enolase 1 differentially contributes to cell transformation in lung cancer but not in esophageal cancer

Abstract

Enolase transforms 2-phospho-D-glycerate into phosphoenolpyruvate during glycolysis. The human enolase (ENO) family comprises three members named ENO3, which is restricted to muscle tissues, ENO2, which is neuron-and neuroendocrine tissue-specific, and ENO1, which is expressed in almost all tissues. ENO1 is involved in various types of human cancer, including retinoblastoma, hepatocellular carcinoma, pancreatic cancer, renal cell carcinoma, cholangiocarcinoma and gastric cancer. Furthermore, ENO1 enhances cell transformation in numerous cancer cell lines. It has been reported that ENO1 is involved in various activities that are detrimental to cell transformation, including apoptosis and differentiation. However, a few studies demonstrated that ENO1 can be downor upregulated in various types of lung cancer, which suggests that ENO1 has an ambiguous role in the development of lung cancer. The present study aimed to investigate the differential influences of ENO1 on various types of cancer, and to clarify the role of ENO1 in lung cancer in particular. Western blotting was performed to assess ENO1 protein expression levels in lung cancer and esophageal cancer tissues. Furthermore, exogenous ENO1 was overexpressed in cell lines derived from various tissues and single cell proliferation, flowcytometric analysis, and western blotting were performed to determine the cell proliferation rate, cell transformation status, cell cycle progression and the expression of cell cycle regulators, such as cyclins and cyclin-dependent kinases, and survival factors, such as MAPK and AKT. The results demonstrated that ENO1 was upregulated in collected panels of lung cancer tissues, but not in esophageal cancer tissues. In addition, overexpression of ectopic ENO1 promoted cell proliferation and survival in lung cancer cell lines, which was not the case in other cells, including an esophageal cell line. Furthermore, mechanistic analyses revealed that ENO1 enhanced cell proliferation by accelerating G 1 progression and upregulating G 1 phase cyclin-dependent kinase 6 (CDK6), and improved cell survival by upregulating p38 in the MAPK cascade and increasing p-AKT in the AKT cascade, in particular in lung cancer cell lines. Overall, the results from the present study demonstrated that ENO1 may contribute to the development of lung cancers, but not esophageal cancers.

Enolase 1 Correlated With Cancer Progression and Immune-Infiltrating in Multiple Cancer Types: A Pan-Cancer Analysis

“…According to previous findings, circ-ENO1 and its host gene ENO1 were upregulated in LUAD cells ( 2 ). ENO1 might also contribute to the progression of lung cancers by stimulating cell proliferation via accelerating G1/S transition, but not in esophageal cancers ( 44 ). Taken together, the varied expression of ENO1 in different types and stages of cancers implied that the effects of ENO1 may vary in different cancers and at different tumor stages.…”

Alpha-Enolase: Emerging Tumor-Associated Antigen, Cancer Biomarker, and Oncotherapeutic Target

“…These functions can be inhibited in cancer cells by ENO1 depletion ( Georges et al, 2011 ; Song et al, 2014 ; Fu et al, 2015 ; Zhu et al, 2015 ; Capello et al, 2016 ; Principe et al, 2017 ; Qian et al, 2017 ; Zhan et al, 2017 ; Qiao et al, 2018a , 2019 ; Ji et al, 2019 ; Sun et al, 2019 ; Wang et al, 2019 ; Xu et al, 2019 ; Santana-Rivera et al, 2020 ), or targeting with antibodies ( Hsiao et al, 2013 ; Principe et al, 2015 ), microRNA (miR) ( Liu et al, 2018 ), or long non-coding RNAs (lncRNAs) ( Yu et al, 2018 ). ENO1 also regulates oncogenic signaling pathways, including PI3K/Akt ( Fu et al, 2015 ; Sun et al, 2019 ; Chen et al, 2020 ; Zang et al, 2020 ), v/β-3 integrin ( Principe et al, 2017 ), β-catenin ( Ji et al, 2019 ), transforming growth factor beta ( Xu et al, 2019 ), AMPK/mTOR ( Zhan et al, 2017 ; Dai et al, 2018 ), and others ( Huang et al, 2019 ).…”

“…Alpha-enolase is overexpressed in multiple human cancer types, contributing to increased glycolysis and tumor growth ( Altenberg and Greulich, 2004 ; Chang et al, 2006 ; He et al, 2007 ; Tsai et al, 2010 ; Capello et al, 2011 ; Song et al, 2014 ; Fu et al, 2015 ; Sun et al, 2017 , 2019 ; Zhan et al, 2017 ; Yin et al, 2018 ; Zhang et al, 2018 , 2020 ; Cheng et al, 2019 ; Ji et al, 2019 ; Qiao et al, 2019 ; Xu et al, 2019 ; Chen et al, 2020 ). ENO1 overexpression is often associated with anti-ENO1 autoantibody responses and may have prognostic and diagnostic value in certain cancers ( Table 1 ; Adamus et al, 1998 ; Tomaino et al, 2011 ; Pranay et al, 2013 ; Hsiao et al, 2015 ; Griggio et al, 2017 ; Zhang et al, 2020 ).…”

α-Enolase Lies Downstream of mTOR/HIF1α and Promotes Thyroid Carcinoma Progression by Regulating CST1

“…Upregulation of ENO1 was detected in cancers of the stomach, breast, lung, colorectal, brain, kidney, liver, pancreas, and eye, as well as in non-Hodgkin's lymphoma (Nakajima et al, 1986;Tu et al, 2010;Song et al, 2014;Fu et al, 2015;Liu et al, 2015;Principe et al, 2015;Zhu et al, 2015Zhu et al, , 2018Niccolai et al, 2016;Qian et al, 2017;Zhan et al, 2017). Ectopic ENO1 overexpression promoted tumor formation and tumor chemoresistance (Tu et al, 2010;Song et al, 2014;Fu et al, 2015;Principe et al, 2017;Qian et al, 2017;Zhan et al, 2017;Sun et al, 2019;Chen et al, 2020). Conversely, ENO1 silencing in tumor cells significantly decreased malignant biological behavior (Fu et al, 2015;Principe et al, 2015;Zhao et al, 2015;Capello et al, 2016;Cappello et al, 2017;Huang et al, 2019).…”