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PODXL promotes malignant progression of hepatocellular carcinoma by activating PI3K/AKT pathway

J Mol Histol. 2024 Dec;55(6):1107-1120. doi: 10.1007/s10735-024-10253-x. Epub 2024 Aug 28.

Abstract

Hepatocellular carcinoma (HCC) presents challenges due to inadequate early monitoring and diagnostic precision, resulting in rising incidence and mortality rates. Identifying reliable predictive biomarkers is imperative. This study investigates PODXL expression in HCC and its mechanisms in tumor onset and progression. Clinical samples were analyzed for PODXL expression in HCC tissues, correlating with clinical features and prognosis. In vitro experiments and bioinformatics analysis validated PODXL's role in HCC, particularly in HCCLM3 cells, highlighting its impact on proliferation, invasion, and metastasis. Enhanced PODXL expression, associated with poor prognosis, was observed in HCC tissues and cells. Downregulating PODXL reduced HCCLM3 cell proliferation, invasion, and migration, while promoting apoptosis. Bioinformatics analysis linked abnormal PODXL expression to the PI3K/AKT pathway. Moreover, PODXL downregulation and PI3K/AKT activation verified PODXL's role in promoting HCCLM3 cell progression via this pathway. This study underscores PODXL's significance in HCC prognosis and suggests its potential as a diagnostic or therapeutic target.

Keywords: Biomarker; Hepatocellular carcinoma (HCC); PI3K/AKT signaling pathway; PODXL; Prognosis.

MeSH terms

  • Apoptosis
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation*
  • Disease Progression*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / pathology
  • Male
  • Middle Aged
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction*

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases