STAT5A modulates gastric cancer progression via upregulation of CD44

Genomics. 2023 May;115(3):110638. doi: 10.1016/j.ygeno.2023.110638. Epub 2023 May 15.

Abstract

Objective: Signal transduction and transcriptional activator 5A (STAT5A), which has been reported to be frequently phosphorylated in tumors, plays pivotal roles in tumor progression. However, the role of STAT5A in gastric cancer (GC) progression and the downstream targets of STAT5A remain largely unknown.

Methods: The expression of STAT5A and CD44 were assessed. GC cells were treated with altered STAT5A and CD44 to evaluate their biological functions. Nude mice were given injections of genetically manipulated GC cells and growth of xenograft tumors and metastases was measured.

Results: The increased level of p-STAT5A is associated with tumor invasion and poor prognosis in GC. STAT5A promoted GC cell proliferation by upregulating CD44 expression. STAT5A directly binds to the CD44 promoter and promotes its transcription.

Conclusions: The STAT5A/CD44 pathway plays a critical role in GC progression, promising potential clinical applications for improving treatment of GC.

Keywords: CD44; Gastric cancer; P-STAT5A; Transcriptional activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Mice
  • Mice, Nude
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism
  • Signal Transduction
  • Stomach Neoplasms* / genetics
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / genetics
  • Up-Regulation

Substances

  • Transcription Factors
  • CD44 protein, human
  • Hyaluronan Receptors
  • STAT5A protein, human
  • Tumor Suppressor Proteins
  • STAT5 Transcription Factor