Cold-shock Domain Protein A (CSDA) Influences Hepatocyte Growth Factor-medicated Cell Proliferation and Metastasis in Gastric Cancer Cells

Anticancer Res. 2024 May;44(5):1973-1981. doi: 10.21873/anticanres.17000.

Abstract

Background/aim: A role for cold-shock domain (CSD) proteins in abnormal cell proliferation has been suggested in the literature. The aim of this study was to investigate the effect of hepatocyte growth factor (HGF)-induced up-regulation of CSD protein A (CSDA) expression on vascular endothelial growth factor (VEGF) expression and its role in gastric cancer cell invasion and proliferation.

Materials and methods: We assessed effects on two gastric cancer cell lines using reverse transcription-polymerase chain reaction, western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and CSDA knockdown with short hairpin RNA.

Results: Hepatocyte growth factor (HGF) elevates CSDA levels in gastric cancer cell lines. To elucidate the mechanism by which HGF prompts CSDA expression and its impact on vascular endothelial growth factor (VEGF), we applied the Mitogen Activated Protein Kinase (MAPK) inhibitor PD098059 and conducted analyses using western blot. Following the administration of PD098059, a reduction in the protein levels of HGF-stimulated VEGF was observed. Additionally, silencing of CSDA resulted in diminished levels of both VEGF and phosphorylated extracellular signal-regulated kinase (ERK). The suppression of CSDA also led to reduced HGF-induced cell proliferation and diminished invasive capabilities in vitro. Furthermore, our research pinpointed a potential activator protein-1 (AP-1) binding site within the VEGF promoter zone, validating its activity via chromatin immunoprecipitation assays. Electrophoretic mobility shift assays further disclosed that HGF-induced CSDA augmentation correlates with an increase in AP-1 binding to VEGF.

Conclusion: CSDA is crucial for the proliferation of gastric cancer cells, and the inhibition of this protein could impede the advancement of gastric cancer.

Keywords: CSDA; Cold-shock domain protein A; cancer proliferation; gastric cancer; target gene.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hepatocyte Growth Factor* / genetics
  • Hepatocyte Growth Factor* / metabolism
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Proteinase Inhibitory Proteins, Secretory*
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / pathology
  • Vascular Endothelial Growth Factor A* / genetics
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Hepatocyte Growth Factor
  • Vascular Endothelial Growth Factor A
  • SPINT1 protein, human
  • HGF protein, human
  • VEGFA protein, human
  • Proteinase Inhibitory Proteins, Secretory