Retinoic Acid–Related Orphan Receptor C Regulates Proliferation, Glycolysis, and Chemoresistance via the PD-L1/ITGB6/STAT3 Signaling Axis in Bladder Cancer
| العنوان: | Retinoic Acid–Related Orphan Receptor C Regulates Proliferation, Glycolysis, and Chemoresistance via the PD-L1/ITGB6/STAT3 Signaling Axis in Bladder Cancer |
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| المؤلفون: | Yongqiang Huang, Bo Dai, Junlong Wu, Xin Hu, Haoran Li, Ziliang Wang, Yangyang Pang, Huyang Xie, Dingwei Ye, Dalong Cao, Yijun Shen, Yao Zhu, Yiping Zhu, Zihao Qi |
| المصدر: | Cancer Research. 79:2604-2618 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, STAT3 Transcription Factor, 0301 basic medicine, Cancer Research, Integrin beta Chains, Retinoic acid, B7-H1 Antigen, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, RAR-related orphan receptor gamma, Humans, STAT3, Aged, Cell Proliferation, Aged, 80 and over, Orphan receptor, biology, Chemistry, Cell growth, Middle Aged, Nuclear Receptor Subfamily 1, Group F, Member 3, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Urinary Bladder Neoplasms, Oncology, Drug Resistance, Neoplasm, Tumor progression, Apoptosis, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Female, Cisplatin, Neoplasm Recurrence, Local, Signal transduction, Glycolysis, Signal Transduction |
| الوصف: | 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 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 recurrence. Significance: These findings suggest that RORC-mediated regulation of a PD-L1/ITGB6/FAK/STAT3 signaling axis in bladder cancer provides several potential therapeutic targets to prevent tumor progression. |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::551963444b881d562315e9a8bbe421a5Test https://doi.org/10.1158/0008-5472.can-18-3842Test |
| رقم الانضمام: | edsair.doi.dedup.....551963444b881d562315e9a8bbe421a5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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