Sorcin promotes proliferation of hepatocellular carcinoma by regulating VEGFA/B via PI3K pathway

J Physiol Biochem. 2024 May;80(2):381-392. doi: 10.1007/s13105-024-01011-4. Epub 2024 Mar 27.

Abstract

Hepatocellular carcinoma (HCC) is a highly vascularized tumor, one of the most common and lethal cancer-related tumor deaths worldwide, with cell proliferation playing a key role. In this study our western blot results and data from TAGC demonstrate a strong association between Sorcin (SRI) overexpression and poor outcomes in HCC. Moreover, SRI overexpression was remarkably effective in promoting proliferation in vitro and increasing tumor growth in vivo, which were attenuated by knocking down SRI. Mechanistically, SRI regulated vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor B (VEGFB) through PI3K/Akt/FOXO1 signal pathway. Overall, our study indicates that SRI stimulates HCC growth by controlling VEGFA/B, which presents a fresh insight into the pathogenesis of hepatocarcinogenesis and a new therapeutic target for HCC.

Keywords: Hepatocellular carcinoma; Proliferation; SRI; VEGFA; VEGFB.

MeSH terms

  • Animals
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Proliferation*
  • Female
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • Vascular Endothelial Growth Factor A* / genetics
  • Vascular Endothelial Growth Factor A* / metabolism
  • Vascular Endothelial Growth Factor B* / genetics
  • Vascular Endothelial Growth Factor B* / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor B
  • Phosphatidylinositol 3-Kinases
  • Calcium-Binding Proteins
  • Proto-Oncogene Proteins c-akt
  • VEGFB protein, human
  • Forkhead Box Protein O1
  • FOXO1 protein, human