PHOSPHATE exporter XPR1/SLC53A1 is required for the tumorigenicity of epithelial ovarian cancer

Cancer Sci. 2022 Jun;113(6):2034-2043. doi: 10.1111/cas.15358. Epub 2022 Apr 24.

Abstract

Ovarian cancer is the fifth most common cause of cancer-related death in women. Ovarian clear cell carcinoma (OCCC) is a chemotherapy-resistant epithelial ovarian cancer with poor prognosis. As a basis for the development of therapeutic agents that could improve the prognosis of OCCC, we performed a screen for proteins critical for the tumorigenicity of OCCC using the CRISPR/Cas9 system. Here we show that knockdown of the phosphate exporter XPR1/SLC53A1 induces the growth arrest and apoptosis of OCCC cells in vitro. Moreover, we show that knockdown of XPR1/SLC53A1 inhibits the proliferation of OCCC cells xenografted into immunocompromised mice. These results suggest that XPR1/SLC53A1 plays a critical role in the tumorigenesis of OCCC cells. We speculate that XPR1/SLC53A1 might be a promising molecular target for the therapeutic treatment of OCCC.

Keywords: XPR1; apoptosis; ovarian cancer; phosphate transporter; proliferation; tumorigenicity.

MeSH terms

  • Adenocarcinoma, Clear Cell* / pathology
  • Animals
  • Carcinoma, Ovarian Epithelial / genetics
  • Female
  • Humans
  • Mice
  • Ovarian Neoplasms* / pathology
  • Phosphates / therapeutic use
  • Prognosis

Substances

  • Phosphates