Hypoxia drives CBR4 down‐regulation promotes gastroenteropancreatic neuroendocrine tumors via activation mammalian target of rapamycin mediated by fatty acid synthase

• DOI: 10.1002/ccs3.12041
• Publication Date: 2024-06-22T14:18:25Z
• Authors: Mujie Ye; Lin Xu; Feiyu Lu; Lingyi Chen; Chunhua Hu; Jinhao Chen; Bingyan Xue; Danyang Gu; Ruitong Xu; Yanling Xu; Ping Yu; Yan Wang; Ye Tian; Guoqin Zhu; Qiyun Tang
• Keywords: Intravasation; Hypoxia

Abstract Hypoxia has been highly proven a hallmark of tumor micro‐environment, promoting the malignant phenotypes, playing crucial role from initiation, progression, invasion, and intravasation to metastatic dissemination outgrowth. Increasing evidence also showed that hypoxia mediated abnormal lipid metabolism in cancer by regulating various oncogenic signal pathways. However, it is still unclear but attractive how specifically functioned changed condition micro‐environment. In present study, we find promoted methylation degree CBR4 promoter region thus downgraded expression , which GEP‐NETs progression increased sensitivity cells everolimus. Further, interacted with fatty acid synthase (FASN), displaying down‐regulation FASN activating ubiquitin proteasome pathway suppressed mTOR signaling. Overall, our results uncovers CBR4/FASN/mTOR axis as mechanism for development inspires us new molecular guide therapeutic strategies treatment.