PD-L1 regulates tumorigenesis and autophagy of ovarian cancer by activating mTORC signaling

Biosci Rep. 2019 Dec 20;39(12):BSR20191041. doi: 10.1042/BSR20191041.

Abstract

PD-L1 is a well-known immune co-stimulatory molecule that regulates tumour cell escape from immunity by suppressing the immune response. However, the clinical significance of PD-L1 in the progression of ovarian cancer is unclear. Our study demonstrated that PD-L1 is up-regulated in ovarian tumour tissue compared with its expression level in adjacent normal tissue. Furthermore, we confirmed that PD-L1 increases the proliferation of cancer cells by activating the AKT-mTORC signalling pathway, which is also enhanced by the expression of S6K, the substrate of mTORC. In addition, PD-L1 promotes the autophagy of ovarian cancer cells by up-regulating the expression of BECN1, a crucial molecule involved in the regulation of autophagy. In conclusion, PD-L1 may provide a target for the development of a novel strategy for the treatment of ovarian cancer.

Keywords: PD-L1; autophagy; mTORC; ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / genetics*
  • B7-H1 Antigen / genetics*
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Interferon-gamma / genetics
  • Mechanistic Target of Rapamycin Complex 1 / genetics
  • Ovarian Neoplasms / genetics*
  • Ribosomal Protein S6 Kinases, 70-kDa / genetics
  • Signal Transduction / genetics

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • IFNG protein, human
  • Interferon-gamma
  • Mechanistic Target of Rapamycin Complex 1
  • Ribosomal Protein S6 Kinases, 70-kDa
  • ribosomal protein S6 kinase, 70kD, polypeptide 1