Reduced IQGAP2 Promotes Bladder Cancer through Regulation of MAPK/ERK Pathway and Cytokines

Int J Mol Sci. 2022 Nov 4;23(21):13508. doi: 10.3390/ijms232113508.

Abstract

The progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is a major challenge in urologic oncology. However, understanding of the molecular processes remains limited. The dysregulation of IQGAP2 is becoming increasingly evident in most tumor entities, and it plays a role in multiple oncogenic pathways, so we evaluated the role of IQGAP2 in bladder cancer. IQGAP2 was downregulated in tumors compared with normal urothelium tissues and cells. IQGAP2 effectively attenuated bladder cancer cell growth independently from apoptosis. Reduced IQGAP2 promoted EMT in bladder cancer cells via activation of the MAPK/ERK pathway. In addition, IQGAP2 might influence key cellular processes, such as proliferation and metastasis, through the regulation of cytokines. In conclusion, we suggest that IQGAP2 plays a tumor-suppressing role in bladder cancer, possibly via inhibiting the MAPK/ERK pathway and reducing cytokines.

Keywords: IQGAP2; MEK/ERK signaling; bladder cancer; cancer progression; tumor suppressor.

MeSH terms

  • Cell Line, Tumor
  • Cytokines / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinases / metabolism
  • Urinary Bladder Neoplasms* / metabolism
  • Urothelium / pathology
  • ras GTPase-Activating Proteins / genetics
  • ras GTPase-Activating Proteins / metabolism

Substances

  • Cytokines
  • IQGAP2 protein, human
  • ras GTPase-Activating Proteins
  • Mitogen-Activated Protein Kinases