Retinol dehydrogenase 10 contributes to cancer stemness and intracellular carbohydrate storage in ovarian clear cell carcinomas

Cancer Biomark. 2022;34(4):673-679. doi: 10.3233/CBM-210435.

Abstract

Background: Ovarian clear cell carcinomas (OCCCs) have been recurrent and refractory among the present treatments, so novel therapeutics are urgently needed.

Objective: The present study accumulates the proof of concept to examine the feasibility of RDH10 as a therapeutic target for treating OCCCs.

Methods: Immunohistochemically, RDH10 expression was evaluated in 111 primary epithelial ovarian cancers, including 55 OCCCs, 31 ovarian endometrioid carcinomas and 25 ovarian serous carcinomas. The spherogenecity provoked by RDH10 was evaluated in OCCC cells. To analyze whether RDH10 promotes carbohydrate storage via the vitamin A-gluconeogenesis pathway, phosphoenolpyruvate carboxykinase 1 (PCK1) protein levels and intracellular carbohydrate content were measured in response to modified RDH10 expression.

Results: Abundant RDH10 was expressed specifically in OCCCs. RDH10 promoted spherogenecity and intracellular carbohydrate storage via modulation of PCK1 expression in OCCC cells.

Conclusions: In the present study, abundant RDH10 contributed to cancer cell stemness and intracellular carbohydrate storage in OCCCs. RDH10 is a potentially, new therapeutic candidate for treating OCCC cases.

Keywords: Ovarian clear cell carcinoma; RDH10; carbohydrates; gluconeogenesis; retinoids.

MeSH terms

  • Adenocarcinoma, Clear Cell* / metabolism
  • Alcohol Oxidoreductases* / metabolism
  • Carbohydrate Metabolism*
  • Female
  • Humans
  • Neoplastic Stem Cells*
  • Ovarian Neoplasms* / metabolism

Substances

  • Alcohol Oxidoreductases
  • trans-retinol dehydrogenase
  • retinol dehydrogenase