title: TRAIL-induced miR-146a expression suppresses CXCR4-mediated human breast cancer migration.
abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered a promising agent for cancer therapy, as this molecule induces apoptosis specifically in various cancer cells. Apart from apoptosis, TRAIL also induces non-apoptotic signals, such as those for autophagy, proliferation and metastasis in cancer cells. In the present study, we report that TRAIL suppressed CXCR4-mediated human breast cancer MDA-MB-231 cell migration by up-regulating miR-146a expression through NF-κB. TRAIL receptor 1 (TRAIL-R1, DR4) was highly expressed in TRAIL-treated MDA-MB-231 cells. A neutralization antibody against DR4 specifically blocked TRAIL-induced NF-κB activation and miR-146a expression. These results were confirmed in a human breast cancer xenograft mouse model, suggesting that TRAIL significantly enhanced miR-146a expression and suppressed CXCR4 expression, indicating that TRAIL-induced miR-146a up-regulation is negatively associated with CXCR4 expression. These findings suggest that TRAIL-induced miR-146a expression suppresses CXCR4-mediated human breast cancer migration, and provide further insight into the non-apoptotic function of TRAIL in the prevention of metastasis as a therapy for breast cancer.
authors: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors: Dongsheng
authors: D
authors: Wang
authors: Dan
authors: D
authors: Liu
authors: Jing
authors: J
authors: Gao
authors: Min
authors: M
authors: Liu
authors: Shilian
authors: S
authors: Liu
authors: Minghong
authors: M
authors: Jiang
authors: Yanxin
authors: Y
authors: Liu
authors: Dexian
authors: D
authors: Zheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology* / Q000502:physiology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C527276:CXCR4 protein, human; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D019718:Receptors, CXCR4; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human
keywords: CXCR4; TRAIL; breast cancer; miR-146a; migration