TCF7L2 promotes anoikis resistance and metastasis of gastric cancer by transcriptionally activating PLAUR

Int J Biol Sci. 2022 Jul 11;18(11):4560-4577. doi: 10.7150/ijbs.69933. eCollection 2022.

Abstract

Gastric cancer (GC) is the most common gastrointestinal malignant tumor, and distant metastasis is a critical factor in the prognosis of patients with GC. Understanding the mechanism of GC metastasis will help improve patient prognosis. Studies have confirmed that urokinase-type plasminogen activator receptor (PLAUR) promotes GC metastasis; however, its relationship with anoikis resistance and associated mechanisms remains unclear. In this study, we demonstrated that PLAUR promotes the anoikis resistance and metastasis of GC cells and identified transcription Factor 7 Like 2 (TCF7L2) as an important transcriptional regulator of PLAUR. We also revealed that TCF7L2 is highly expressed in GC and promotes the anoikis resistance and metastasis of GC cells. Moreover, we found that TCF7L2 transcription activates PLAUR. Finally, we confirmed that TCF7L2 is an independent risk factor for poor prognosis of patients with GC. Our results show that TCF7L2 and PLAUR are candidate targets for developing therapeutic strategies for GC metastasis.

Keywords: anoikis; gastric cancer; transcription; transcription Factor 7 Like 2; urokinase-type plasminogen activator receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anoikis*
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Metastasis / genetics
  • Plasminogen Activators
  • Receptors, Urokinase Plasminogen Activator* / genetics
  • Signal Transduction
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / pathology
  • Transcription Factor 7-Like 2 Protein* / genetics

Substances

  • PLAUR protein, human
  • Receptors, Urokinase Plasminogen Activator
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • Plasminogen Activators