Abstract
Simple SummaryAlpha-enolase (ENO1) undergoes accentuated overexpression in several solid cancers, but little is known about its status in cutaneous melanoma. The aim of this study was to investigate the prognostic significance of ENO1 in surgical resections from melanoma patients and to assess its expression and enzymatic activity in several melanoma cell lines. In clinical analysis, the overexpression of ENO1 in melanoma cells was significantly correlated with advanced clinical stage, presence of metastases in regional lymph nodes, and shorter cancer-specific overall survival and disease-free survival. We also demonstrated high expression of ENO1 in melanoma cell lines compared with normal melanocytes. Our study, which extends previous in vitro research, makes the alpha-enolase a candidate for a promising diagnostic and therapeutic target for various types of cancers. Consequently, additional testing of ENO1 as a target for melanoma therapy is necessary.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.
Highlights
Cutaneous melanoma (CM) is an aggressive skin cancer whose incidence varies considerably between racial and ethnic groups of people
We analyzed the expression of ENO1 in four cell lines—two derived from the primary tumor (A375 and WM1341D), and two from lymph node metastases (Hs294T and WM9)
We observed a statistically significant (p = 0.001) upregulation of ENO1 in the WM9 cell line in comparison with the primary human epidermal melanocytes (Figure 1). This expression pattern of ENO1 positively correlated with estimated population doubling times of examined melanoma cell lines
Summary
Cutaneous melanoma (CM) is an aggressive skin cancer whose incidence varies considerably between racial and ethnic groups of people. It is generally lower in people with highly pigmented skin chronically exposed to the sun. Characterizing novel therapeutic targets involved in CM resistance to chemo- and immunotherapies may help to design new therapeutic strategies One of such promising targets is alpha-enolase (ENO1, EC 4.2.1.11) [9]. It is an evolutionary conserved, glycolytic metalloenzyme responsible for the reversible dehydration of 2-phospho-D-glycerate to phosphoenolpyruvate. An increase in ENO1 expression accompanies numerous human diseases (e.g., rheumatoid arthritis, systemic sclerosis, lupus erythematosus, Alzheimer’s disease), including over 18 classes of solid and hematological cancers [11,12,13,14,15]
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