PMID- 25115395 OWN - NLM STAT- MEDLINE DCOM- 20150806 LR - 20211203 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 5 IP - 17 DP - 2014 Sep 15 TI - Aurora kinase a suppresses metabolic stress-induced autophagic cell death by activating mTOR signaling in breast cancer cells. PG - 7498-511 AB - Aberrant Aur-A signaling is associated with tumor malignant behaviors. However, its involvement in tumor metabolic stress is not fully elucidated. In the present study, prolonged nutrient deprivation was conducted into breast cancer cells to mimic metabolic stress in tumors. In these cells, autophagy was induced, leading to caspase-independent cell death, which was blocked by either targeted knockdown of autophagic gene ATG5 or autophagy inhibitor 3-Methyladenine (3-MA). Aur-A overexpression mediated resistance to autophagic cell death and promoted breast cancer cells survival when exposed to metabolic stress. Moreover, we provided evidence that Aur-A suppressed autophagy in a kinase-dependent manner. Furthermore, we revealed that Aur-A overexpression enhanced the mammalian target of rapamycin (mTOR) activity under metabolic stress by inhibiting glycogen synthase kinase 3beta (GSK3beta). Inhibition of mTOR activity by rapamycin sensitized Aur-A-overexpressed breast cancer cells to metabolic stress-induced cell death. Consistently, we presented an inverse correlation between Aur-A expression (high) and autophagic levels (low) in clinical breast cancer samples. In conclusion, our data provided a novel insight into the cyto-protective role of Aur-A against metabolic stress by suppressing autophagic cell death, which might help to develop alternative cell death avenues for breast cancer therapy. FAU - Xu, Ling-Zhi AU - Xu LZ AD - Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. FAU - Long, Zi-Jie AU - Long ZJ AD - Department of Hematology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Institute of Hematology, Sun Yat-sen University, Guangzhou, China. FAU - Peng, Fei AU - Peng F AD - Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. FAU - Liu, Yang AU - Liu Y AD - Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. FAU - Xu, Jie AU - Xu J AD - Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. FAU - Wang, Chang AU - Wang C AD - Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. FAU - Jiang, Lei AU - Jiang L AD - Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. FAU - Guo, Tao AU - Guo T AD - Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. FAU - Kamran, Muhammad AU - Kamran M AD - Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. FAU - Li, Si-Si AU - Li SS AD - Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. FAU - Wang, Chun-Li AU - Wang CL AD - Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. FAU - Wang, Hong-Jiang AU - Wang HJ AD - Department of Breast Surgery, the First Affiliated Hospital, Dalian Medical University, Dalian, China. FAU - Zhao, Yong-Fu AU - Zhao YF AD - Department of Thyroid Surgery, the Second Affiliated Hospital, Dalian Medical University, Dalian, China. FAU - Wan, Xian-Yao AU - Wan XY AD - Department of Critical Care Medicine, the First Affiliated Hospital, Dalian Medical University, Dalian, China. FAU - Liu, Quentin AU - Liu Q AD - Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. Department of Hematology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Institute of Hematology, Sun Yat-sen University, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (RNA, Small Interfering) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (AURKA protein, human) RN - EC 2.7.11.1 (Aurora Kinase A) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Apoptosis/*physiology MH - Aurora Kinase A/*metabolism MH - Blotting, Western MH - Breast Neoplasms/metabolism/*pathology MH - Cell Line, Tumor MH - Comet Assay MH - Female MH - Fluorescent Antibody Technique MH - Humans MH - Microscopy, Electron, Transmission MH - RNA, Small Interfering MH - Signal Transduction/physiology MH - Stress, Physiological/*physiology MH - TOR Serine-Threonine Kinases/*metabolism MH - Transfection MH - Tumor Cells, Cultured PMC - PMC4202139 COIS- Conflict of Interest No potential conflicts of interest were disclosed. EDAT- 2014/08/15 06:00 MHDA- 2015/08/08 06:00 PMCR- 2014/09/01 CRDT- 2014/08/14 06:00 PHST- 2014/08/14 06:00 [entrez] PHST- 2014/08/15 06:00 [pubmed] PHST- 2015/08/08 06:00 [medline] PHST- 2014/09/01 00:00 [pmc-release] AID - 2241 [pii] AID - 10.18632/oncotarget.2241 [doi] PST - ppublish SO - Oncotarget. 2014 Sep 15;5(17):7498-511. doi: 10.18632/oncotarget.2241.