FAM83A has a pro-tumor function in ovarian cancer by affecting the Akt/Wnt/β-catenin pathway

Environ Toxicol. 2022 Apr;37(4):695-707. doi: 10.1002/tox.23435. Epub 2021 Dec 21.

Abstract

Family with sequence similarity 83, member A (FAM83A) is a tumor-exclusive gene that has a vital role in numerous tumors. However, its role in tumorigenesis remains controversial. This work is dedicated to the study of the role of FAM83A in ovarian cancer. We observed elevated levels of FAM83A in ovarian cancer specimens and cells. Kaplan-Meier survival curves revealed that elevated FAM83A levels predicted a worse overall survival in ovarian cancer patients. The inhibition of FAM83A caused remarkable suppressive effects on the proliferation and invasion of ovarian cancer cells, and enhanced their chemosensitivity. On the contrary, the upregulation of FAM83A had opposite effects. Mechanistically, FAM83A had an effect on the Akt and Wnt/β-catenin pathways in ovarian cancer cells. The repression of Akt could cancel the regulatory effect of FAM83A overexpression on the Wnt/β-catenin pathway. Moreover, reactivation of the Wnt/β-catenin pathway abolished FAM83A-inhibition-evoked antitumor effects. Additionally, FAM83A inhibition weakened the tumorigenic potential of ovarian cancer in vivo. Taken together, this work shows that FAM83A exerts a pro-tumor function in ovarian cancer by affecting the Akt/Wnt/β-catenin pathway and proposes FAM83A as an effective and possible treatment target for ovarian cancer.

Keywords: Akt; FAM83A; Wnt; ovarian cancer.

MeSH terms

  • Carcinogenesis / genetics
  • Female
  • Humans
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / physiology
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Wnt Signaling Pathway
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • FAM83A protein, human
  • Neoplasm Proteins
  • beta Catenin
  • Proto-Oncogene Proteins c-akt