PMID- 27460085 OWN - NLM STAT- MEDLINE DCOM- 20170206 LR - 20211203 IS - 1423-0380 (Electronic) IS - 1010-4283 (Linking) VI - 37 IP - 10 DP - 2016 Oct TI - Alternative splicing of S6K1 promotes non-small cell lung cancer survival. PG - 13369-13376 AB - Ribosomal S6 kinase 1 (S6K1) that acts downstream of the mammalian target of rapamycin (mTOR) plays an important role in cell proliferation, protein translation, and cell survival. The gene RPS6KB1 encoding for S6K1 had been found to be alternatively spliced to form different isoforms. In this study, we identified that short isoforms of S6K1 splice variant were overproduced in non-small cell lung cancer (NSCLC). Moreover, suppression of S6K1 short isoforms inhibited NSCLC cell growth and induced apoptosis via upregulation of the BH3-only protein Bim in vitro and in vivo. Additionally, short isoforms of S6K1 activated mTORC1, leading to increased 4E-BP1 phosphorylation. Taken together, our findings suggested that S6K1 short isoforms were deregulated in NSCLC and promoted cell survival. Altogether, our study opens possibilities of new therapeutic approaches for NSCLC that selectively downregulate S6K1 shorter isoforms. FAU - Mei, Hong AU - Mei H AD - Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, China. FAU - Wang, Ye AU - Wang Y AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, China. FAU - Fan, Jiquan AU - Fan J AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, China. FAU - Lin, Zhenyu AU - Lin Z AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, China. 15827130393@163.com. LA - eng PT - Journal Article DEP - 20160727 PL - Netherlands TA - Tumour Biol JT - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JID - 8409922 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Bcl-2-Like Protein 11) RN - 0 (Cell Cycle Proteins) RN - 0 (EIF4EBP1 protein, human) RN - 0 (Multiprotein Complexes) RN - 0 (Phosphoproteins) RN - 0 (RNA, Small Interfering) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1) SB - IM MH - Adaptor Proteins, Signal Transducing/metabolism MH - *Alternative Splicing MH - Animals MH - Bcl-2-Like Protein 11/genetics/metabolism MH - Carcinoma, Non-Small-Cell Lung/*genetics/metabolism/pathology MH - Cell Cycle Proteins MH - Cell Line, Tumor MH - Cell Proliferation MH - Cell Survival/genetics MH - Disease Models, Animal MH - Female MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic MH - Gene Knockdown Techniques MH - Humans MH - Lung Neoplasms/*genetics/metabolism/pathology MH - Mechanistic Target of Rapamycin Complex 1 MH - Mice MH - Multiprotein Complexes MH - Oncogenes MH - Phosphoproteins/metabolism MH - Protein Binding MH - RNA, Small Interfering/genetics MH - Ribosomal Protein S6 Kinases, 70-kDa/*genetics MH - TOR Serine-Threonine Kinases MH - Xenograft Model Antitumor Assays OTO - NOTNLM OT - Alternative splicing OT - Cell survival OT - Non-small cell lung cancer OT - Ribosomal S6 kinase 1 EDAT- 2016/07/28 06:00 MHDA- 2017/02/07 06:00 CRDT- 2016/07/28 06:00 PHST- 2016/03/20 00:00 [received] PHST- 2016/07/15 00:00 [accepted] PHST- 2016/07/28 06:00 [pubmed] PHST- 2017/02/07 06:00 [medline] PHST- 2016/07/28 06:00 [entrez] AID - 10.1007/s13277-016-5253-1 [pii] AID - 10.1007/s13277-016-5253-1 [doi] PST - ppublish SO - Tumour Biol. 2016 Oct;37(10):13369-13376. doi: 10.1007/s13277-016-5253-1. Epub 2016 Jul 27.