CADM1 inhibits ovarian cancer cell proliferation and migration by potentially regulating the PI3K/Akt/mTOR pathway

Biomed Pharmacother. 2020 Mar:123:109717. doi: 10.1016/j.biopha.2019.109717. Epub 2019 Dec 25.

Abstract

Previous studies have shown that cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is frequently inactivated but functions as a tumor suppressor in many solid tumors. However, the characterization of CADM1 expression in ovarian cancer cells and the mechanisms of its tumor suppressor function are not fully understood. We generated ovarian cancer cell lines in which CADM1 was stably upregulated or downregulated. CADM1 expression was significantly decreased in ovarian cancer tissue and cells lines. Functionally, knockdown of CADM1 promoted the growth, migration and invasion of ovarian cancer cells. Conversely, further experimental evidence indicated that overexpression of CADM1 inhibited the migration and invasion of ovarian cancer cells potentially through inhibition of the PI3K/Akt/mTOR signaling pathway by regulating upstream regulators (LXR/RXR, IGF1, IFI44L and C4BPA) and downstream effectors (APP, EDN1, TGFBI and Rap1A). In conclusion, CADM1 inhibits ovarian cancer cell proliferation and migration by potentially regulating the PI3K/Akt/mTOR signaling pathway. CADM1 could be a potential therapeutic target for ovarian cancer.

Keywords: Cell adhesion molecule 1; Invasion; Migration; Ovarian cancer; PI3K/Akt/mTOR.

MeSH terms

  • Cell Adhesion Molecule-1 / genetics
  • Cell Adhesion Molecule-1 / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Down-Regulation
  • Epithelial Cells
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Silencing
  • Humans
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Transcriptome

Substances

  • CADM1 protein, human
  • Cell Adhesion Molecule-1
  • RNA, Messenger
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases