SYNPO2 suppresses hypoxia-induced proliferation and migration of colorectal cancer cells by regulating YAP-KLF5 axis

Tissue Cell. 2021 Dec:73:101598. doi: 10.1016/j.tice.2021.101598. Epub 2021 Jul 26.

Abstract

Colorectal cancer (CRC) is one of the most common tumors that has a high incidence worldwide. Targeted therapy for CRC has received much attention recently. It is still necessary to develop novel and promising therapeutic targets to improve the prognosis. SYNPO2, also known as synapsopoprotein 2 or myopod, encodes actin binding proteins and has been characterized as a tumor suppressor for aggressive cancers. SYNPO2 has been reported to inhibit the activity of YAP/TAZ. However, whether SYNPO2 could regulate the progression of CRC through the YAP/YAZ signaling pathway remains unclear. Herein, it was found that the expression of SYNPO2 was low in hypoxia-exposed CRC cells, consistent with the data from TCGA database. SYNPO2 inhibited the growth of CRC cells upon hypoxia treatment and promoted the cell apoptosis. Additionally, SYNPO2 inhibited the migration and epithelial-mesenchymal transformation (EMT) CRC cell upon hypoxia treatment. Mechanically, the results demonstrated that SYNPO2 suppressed hypoxia-induced progression of CRC by regulating YAP-Kruppel like factor 5 (KLF5) axis. Therefore, SYNPO2 can serve as a promising therapeutic target for CRC treatment.

Keywords: Colorectal cancer (CRC); Epithelial-mesenchymal transformation (EMT); Kruppel like factor 5 (KLF5); Synapsopoprotein 2 (SYNPO2); YAP.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kruppel-Like Transcription Factors / metabolism*
  • Microfilament Proteins / metabolism*
  • Signal Transduction*
  • Tumor Hypoxia* / genetics
  • YAP-Signaling Proteins / metabolism*

Substances

  • KLF5 protein, human
  • Kruppel-Like Transcription Factors
  • Microfilament Proteins
  • SYNPO2 protein, human
  • YAP-Signaling Proteins
  • YAP1 protein, human