title: Targeting MCT-1 oncogene inhibits Shc pathway and xenograft tumorigenicity.
abstract: Overexpression of Shc adaptor proteins is associated with mitogenesis, carcinogenesis and metastasis. Multiple copies in T-cell malignancy 1 (MCT-1) oncoprotein promotes cell proliferation, survival and tumorigenic effects. Our current data show that MCT-1 is a novel regulator of Shc-Ras-MEK-ERK signaling and MCT-1 is significantly co-activated with Shc gene in human carcinomas. The knockdown of MCT-1 enhances apoptotic cell death accompanied with the activation of caspases and cleavage of caspase substrates under environmental stress. The cancer cell proliferation, chemo-resistance and tumorigenic capacity are proved to be effectively suppressed by targeting MCT-1. Accordingly, an important linkage between MCT-1 oncogenicity and Shc pathway in tumor development has now been established. Promoting MCT-1 expression by gene hyperactivation may be recognized as a tumor marker and MCT-1 may serve as a molecular target of cancer therapy.
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan.
authors.forename: Hung-Ju
authors.initials: HJ
authors.lastname: Shih
authors.forename: Hsiao-Huei
authors.initials: HH
authors.lastname: Chen
authors.forename: Yen-An
authors.initials: YA
authors.lastname: Chen
authors.forename: Meng-Hsun
authors.initials: MH
authors.lastname: Wu
authors.forename: Gan-Guang
authors.initials: GG
authors.lastname: Liou
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Chang
authors.forename: Linyi
authors.initials: L
authors.lastname: Chen
authors.forename: Lu-Hai
authors.initials: LH
authors.lastname: Wang
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Hsu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D053148:Caspase 3 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D039663:Integrin beta4 / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D055765:Shc Signaling Adaptor Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D018631:ras Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D039663:Integrin beta4; C115081:MCTS1 protein, human; D015513:Oncogene Proteins; D012333:RNA, Messenger; D055765:Shc Signaling Adaptor Proteins; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D018631:ras Proteins; D017239:Paclitaxel