Overexpression of EPS8L3 promotes cell proliferation by inhibiting the transactivity of FOXO1 in HCC

Neoplasma. 2018 Sep 19;65(5):701-707. doi: 10.4149/neo_2018_170725N503. Epub 2018 Jun 17.


The homology of epidermal growth factor receptor pathway substrate 8 (EPS8), EPS8L3, is elevated significantly in hepatocellular carcinoma (HCC) tissues and cell lines compared with the normal liver tissues and cell lines. The MTT and colony formation assays demonstrated that overexpressing EPS8L3 enhances, while silencing reduces the proliferation of HCC cells. Further experiments illustrated that overexpressing EPS8L3 promotes the expression of p-AKT, Cyclin D1, but inhibits the transcriptional activity of FOXO1. Besides, colony formation assay demonstrated that AKT inhibitor suppresses the effect of EPS8L3 on proliferation in EPS8L3-overexpressing cells, whereas AKT restores the proliferation of EPS8L3-silenced cells, suggesting that EPS8L3 might promote proliferation by hyperactivating the AKT signaling pathway and subsequently inhibiting the FOXO1 transcriptional activity. Our results provide new view between EPS8L3 and progression of human HCC, suggesting that EPS8L3 may be a novel therapeutic target for HCC.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Forkhead Box Protein O1 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*


  • Adaptor Proteins, Signal Transducing
  • EPS8L3 protein, human
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Proto-Oncogene Proteins c-akt