Retinoic acid-related orphan receptor C regulates proliferation, glycolysis, and chemoresistance via the PD-L1/ITGB6/STAT3 signaling axis in bladder cancer

Cancer Research
Dalong CaoZiliang Wang

Abstract

Retinoic acid-related orphan receptor C (RORC) is a member of the nuclear orphan receptor family and performs critical regulatory functions in cell proliferation, metastasis, and chemoresistance in various types of malignant tumors. Here we showed that expression of RORC is lost in tumor tissues of bladder cancer patients. Enhanced expression of RORC suppressed cell proliferation and glucose metabolism and increased cisplatin-induced apoptosis in vitro and in vivo. RORC bound the promoter region of programmed death ligand-1 (PD-L1) and negatively regulated PD-L1 expression. PD-L1 directly interacted with integrin β6 (ITGB6) and activated the ITGB6/FAK signaling pathway. RORC prevented the nuclear translocation of signal transducers and activators of transcription 3 (STAT3) via suppression of the PD-L1/ITGB6 signaling pathway, which further inhibited bladder cell proliferation and glucose metabolism and increased cisplatin-induced apoptosis. These findings reveal that RORC regulates bladder cancer cell proliferation, glucose metabolism, and chemoresistance by participating in the PD-L1/ITGB6/STAT3 signaling axis. Moreover, this new understanding of PD-L1 signaling may guide the selection of therapeutic targets to prevent tumor r...Continue Reading

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Citations

Apr 17, 2020·Thoracic Cancer·Yixiang ZhangQingkai Yang
Jan 1, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sepideh MirzaeiHaroon Khan
Feb 28, 2021·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Lukas Gammelgaard RasmussenSönke Detlefsen
Apr 8, 2021·Acta Pharmacologica Sinica·Fei-Fei XuLi-Hong Ye
May 4, 2021·Biochemical and Biophysical Research Communications·Feikai LinXipeng Wang
Jun 3, 2021·International Journal of Molecular Sciences·Ioannis A VathiotisNikolaos Syrigos
Jul 4, 2021·Experimental and Molecular Pathology·Xingzhe LiuYanhua Xuan
Nov 27, 2021·Journal of Cellular Physiology·Seyed Z RasihashemiParisa Lotfinejad
Jan 16, 2022·Nature Reviews. Cancer·Anand V R KornepatiTyler J Curiel

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