PXMP4 promotes gastric cancer cell epithelial-mesenchymal transition via the PI3K/AKT signaling pathway

Mol Biol Rep. 2024 Feb 24;51(1):350. doi: 10.1007/s11033-024-09312-z.

Abstract

Background: Peroxisomal membrane protein 4 (PXMP4), a member of the peroxisome membrane protein PXMP2/4 family, participates in the progression of several malignant cancers. Nevertheless, the effect of PXMP4 in the development of gastric cancer (GC) is still unknown. As a result, the focus of this investigation was to elucidate the potential mechanisms of PXMP4 in GC.

Methods and results: Firstly, bioinformatics analysis results showed higher expression of PXMP4 in GC tissues. Secondly, clinical analysis of 57 patients with GC revealed correlations between PXMP4 expression and differentiation, depth of invasion, as well as TNM stage. Furthermore, individuals with elevated PXMP4 expression in GC exhibited an unfavorable prognosis. In vitro data showed the involvement of knockdown/overexpression of PXMP4 in the proliferation, invasion, and migration of GC cells, and triggering the epithelial-mesenchymal transition (EMT) of GC cells through the activation of the PI3K/AKT signaling pathway. LY294002, a PI3K/AKT inhibitor, inhibited the expression of PI3K/AKT-related proteins but did not affect the expression of PXMP4.

Conclusions: These findings indicate that PXMP4 potentially functions as an upstream molecule in the PI3K/AKT pathway, governing the EMT process in GC.

Keywords: Epithelial-mesenchymal transition; Gastric cancer; PI3K/AKT; PXMP4.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Membrane Proteins / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt* / genetics
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction
  • Stomach Neoplasms* / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Membrane Proteins
  • PXMP2 protein, human