SIAH2 regulates colorectal cancer tumorigenesis via PI3K/ATK signaling pathway

Tissue Cell. 2022 Oct:78:101878. doi: 10.1016/j.tice.2022.101878. Epub 2022 Jul 29.

Abstract

Colorectal cancer (CRC) is the third most common cancer and the 4th leading cause of cancer-related deaths, although with a dismal prognosis. The SIAH E3 Ubiquitin Protein Ligase 2 (SIAH2) regulates the expression of multiple proteins via ubiquitination and proteasome. However, the biological role of SIAH2 in colorectal cancer tumorigenesis remains controversial. In this work, we found that SIAH2 is an oncogene in colorectal cancer. Moreover, SIAH2 promoted colorectal cancer cell proliferation, migration, invasion, and colony formation. Mechanistically, SIAH2 promoted the PI3K/AKT signaling pathway both in vivo and in vitro. Besides, we discovered that PTEN loss regulates SIAH2-mediated PI3K/AKT signaling pathway activation. In summary, these findings highlight the role of SIAH2 in colorectal cancer progression and provide novel insights for treatment.

Keywords: AKT; Colorectal cancer; PTEN; SIAH2.

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase / metabolism
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic
  • Colorectal Neoplasms* / genetics
  • Humans
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / genetics
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Ubiquitin-Protein Ligases
  • Agammaglobulinaemia Tyrosine Kinase
  • Proto-Oncogene Proteins c-akt
  • Proteasome Endopeptidase Complex