Mst1缺陷增强细胞毒性T细胞功能并抑制肿瘤进展。
Enhanced cytotoxic T-cell function and inhibition of tumor progression by Mst1 deficiency.
作者信息
Yasuda Kaneki, Ueda Yoshihiro, Ozawa Madoka, Matsuda Tadashi, Kinashi Tatsuo
机构信息
Department of Urology and Andrology, Kansai Medical University, Osaka, Japan.
Department of Molecular Genetics, Kansai Medical University, Osaka, Japan.
出版信息
FEBS Lett. 2016 Jan;590(1):68-75. doi: 10.1002/1873-3468.12045. Epub 2016 Jan 4.
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.
哺乳动物类STE-20样激酶Mst1在细胞凋亡、增殖、细胞极性和迁移过程中发挥重要作用。在此，我们报告Mst1在细胞毒性T细胞反应和肿瘤抑制方面的新作用。Mst1缺陷导致FoxO水平降低，并在体外促进细胞毒性。Mst1(-/-)细胞毒性T细胞还表现出T-bet表达增强，这与IFNγ和颗粒酶B表达水平升高有关。此外，Mst1(-/-)细胞毒性T细胞在体内抑制肿瘤生长。数据表明，Mst1通过FoxO1和FoxO3a抑制T-bet来抑制细胞毒性。因此，Mst1是肿瘤免疫治疗的潜在治疗靶点。
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