title: Alternative splicing of S6K1 promotes non-small cell lung cancer survival.
abstract: 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.
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Mei
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, China.
authors.forename: Jiquan
authors.initials: J
authors.lastname: Fan
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, China. 15827130393@163.com.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Lin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D000072224:Bcl-2-Like Protein 11 / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes; D009857:Oncogenes; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072224:Bcl-2-Like Protein 11; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D000076222:Mechanistic Target of Rapamycin Complex 1; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1
keywords: Alternative splicing; Cell survival; Non-small cell lung cancer; Ribosomal S6 kinase 1