title: Enhanced cytotoxic T-cell function and inhibition of tumor progression by Mst1 deficiency.
abstract: Mammalian ste-20 like kinase Mst1 plays important roles during apoptosis, proliferation, cell polarity, and migration. Here, we report a novel role of Mst1 for cytotoxic T-cell responses and tumor suppression. The defect of Mst1 caused decreased levels of FoxO, and promoted cytotoxicity in vitro. Mst1(-/-) cytotoxic T cells also exhibited enhanced T-bet expression that was associated with elevated expression levels of IFNγ and granzyme B. Moreover, Mst1(-/-) cytotoxic T cells suppressed tumor growth in vivo. The data suggest that Mst1 inhibits cytotoxicity via T-bet suppression by FoxO1 and FoxO3a. Thus, Mst1 is a potential therapeutic target for tumor immunotherapy.
authors.affiliation: Department of Urology and Andrology, Kansai Medical University, Osaka, Japan.
authors.forename: Kaneki
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Department of Molecular Genetics, Kansai Medical University, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Molecular Genetics, Kansai Medical University, Osaka, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Ozawa
authors.affiliation: Department of Urology and Andrology, Kansai Medical University, Osaka, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
authors.affiliation: Department of Molecular Genetics, Kansai Medical University, Osaka, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kinashi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D007157:Immunologic Surveillance; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation / Q000276:immunology / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000090742:Serine-Threonine Kinase 3; D013047:Specific Pathogen-Free Organisms; D016019:Survival Analysis; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D047368:Tumor Burden; D000098815:T-bet Transcription Factor; D000099317:Hippo Kinases
chemical_list: D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C474033:FoxO3 protein, mouse; C467200:Foxo1 protein, mouse; C490818:Stk3 protein, mouse; D000099317:Hippo Kinases
keywords: FoxO; Mst1; cytotoxic T cells