ORP5 promotes migration and invasion of cervical cancer cells by inhibiting endoplasmic reticulum stress

Cell Stress Chaperones. 2023 Jul;28(4):395-407. doi: 10.1007/s12192-023-01357-6. Epub 2023 Jun 14.

Abstract

ORP5 is a transmembrane protein anchored to the endoplasmic reticulum, which mainly functions as a lipid transporter and has reportedly been linked to cancer. However, the specific mechanism of ORP5 action in cervical cancer (CC) is unclear. In this study, we found that ORP5 promotes the migration and invasive ability of CC cells in vitro and in vivo. In addition, ORP5 expression was linked to endoplasmic reticulum stress, and ORP5 encouraged CC metastasis by inhibiting endoplasmic reticulum stress. Mechanistically, ORP5 inhibited endoplasmic reticulum stress in CC cells by stimulating ubiquitination and proteasomal degradation of SREBP1 to reduce its expression. In conclusion, ORP5 promotes the malignant progression of CC by inhibiting endoplasmic reticulum stress, providing a therapeutic target and strategy for CC treatment.

Keywords: Cervical cancer; Endoplasmic reticulum stress; ORP5; SREBP1; Ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Endoplasmic Reticulum Stress*
  • Female
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness*
  • Receptors, Steroid* / metabolism
  • Uterine Cervical Neoplasms* / metabolism

Substances

  • oxysterol binding protein
  • Receptors, Steroid
  • SREBF1 protein, human