Ezrin promotes hepatocellular carcinoma progression by modulating glycolytic reprogramming.

Abstract

Ezrin, one of the ezrin‐radixin‐moesin (ERM) proteins, is involved in the formation of cell membrane processes and has been implicated in the promotion of cancer proliferation and metastasis. However, the possible role of ezrin in hepatocellular carcinoma (HCC) metastasis and glycolysis reprogramming has remained unclear. In this study, we found that ezrin was upregulated in HCC tissues, and its overexpression was linked with HCC patients’ aggressive tumor characteristics and poor prognosis. Functional experiments further revealed that ezrin overexpression promoted HCC cell proliferation, epithelial‐to‐mesenchymal transition (EMT) progression and angiogenesis. In addition, by measuring glucose consumption, lactate production, ATP levels and the expression of glucose metabolism‐related markers in HCC cells, we investigated whether ezrin regulated glucose metabolism. Moreover, 2‐deoxy‐D‐glucose (2‐DG) affected ezrin‐mediated proliferation, migration and EMT of HCC cells, which suggested that ezrin may, at least in part, promote HCC progression by regulating glycolysis reprogramming. Based on our results, we proposed that ezrin was involved in HCC progression and may be a valid prognostic marker.