Di-san junyi daxue xuebao (Feb 2022)

Ezrin promotes invasion and metastasis of hepatocellular carcinoma by regulating invadopodia formation

  • ZHENG Bowen,
  • WANG Baolin,
  • LU Yao,
  • HUANG Deng,
  • HUANG Deng,
  • ZHANG Hang,
  • LIU Jialong,
  • ZHENG Shuguo

DOI
https://doi.org/10.16016/j.2097-0927.202111088
Journal volume & issue
Vol. 44, no. 4
pp. 346 – 355

Abstract

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Objective To explore the role of ezrin in the formation of invadopodia in hepatocellular carcinoma (HCC) cells. Methods GEPIA database was used to analyze the expression correlation between ezrin and the invadopodia marker cortactin in HCC tissues at mRNA level. Tissue specimens obtained from 105 HCC patients were made into tissue microarrays, which were subsequently detected by immunohistochemistry to analyze the expression correlation of ezrin with cortactin at protein level. Moreover, the relationship between ezrin level and the clinicopathological features as well as the prognosis of HCC patients were analyzed. Finally, ezrin expression was knocked down or up-regulated in HCC cells, respectively, and Transwell assay was performed to observe the effects of ezrin expression changes on the invasion and migration of HCC cells; Western blotting and immunofluorescence assay were also adopted to detect the role of ezrin in the formation of invadopodia in HCC cells. Results Bioinformatics analysis revealed that the mRNA level of ezrin was positively correlated with that of cortactin in HCC tissues (r=0.420, P < 0.01), and immunohistochemistry assay also confirmed the positive correlation between ezrin and cortactin expression at protein level (r= 0.491, P < 0.001). Analysis of clinical data showed that high expression of ezrin protein was correlated with vascular invasion rate (P=0.016) and tumor-related mortality rate (P=0.018) in HCC patients, and patients with higher ezrin level had both lower 5-year postoperative survival rate and 5-year tumor-free survival rate (P < 0.05). In cell experiments, up-regulation of ezrin promoted the invasion and metastasis (P < 0.05), and facilitated the invadopodia formation of HCC cells (P < 0.05). In contrast, knockdown of ezrin suppressed the invadopodia formation and inhibited the invasion and metastasis of HCC cells. Conclusion Ezrin enhances the invasive and migratory abilities of HCC cells by regulating invadopodia formation and thus promotes the progression of HCC.

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