中山醫學大學機構典藏 CSMUIR:Item 310902500/19277
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    题名: Gab1 is essential for membrane translocation, activity and integrity of mTORCs after EGF stimulation in urothelial cell carcinoma
    作者: CH, Chang
    PC, Chan
    JR, Li
    CJ, Chen
    JJ, Shieh
    YC, Fu
    HC, Chen
    MJ, Wu
    贡献者: 中山醫學大學
    关键词: mTORCs;Gab1;EGF;urothelial carcinoma
    日期: 2015-01
    上传时间: 2018-06-22T03:53:42Z (UTC)
    出版者: 1949-2553
    ISSN: 1949-2553
    摘要: Urothelial carcinoma is the most common type of malignancy in long-term dialysis patients and kidney transplant recipients in Taiwan. mTORCs (mammalian target of rapamycin complexes) and EGF are important in urothelial carcinoma. To identify the regulation of mTORCs upon EGF stimulation is necessary. mTOR integrates signals from growth factors via mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2). The mechanism of mTORC1 action has been widely studied; however, the regulation of mTORC2 has not been well studied. Here, we demonstrate that Gab1 is an important upstream regulator in EGF-mediated activation of mTORCs. In our study, we confirm that mTORCs translocate from the cytoplasm to the plasma membrane via the PH domain of Gab1 upon EGF stimulation. Moreover, Gab1 associates with mTORCs. This association stabilizes the integrity of mTORCs and induces mTORC activity. Compared to normal bladder tissue, the expression of Gab1 and activity of mTORCs are elevated in urothelial carcinoma. Collectively, our results suggest that Gab1 is an essential regulator of the EGF-mediated mTORC pathways and may potentially be used as a biomarker for urothelial carcinoma to predict diagnosis and drug response.
    URI: http://dx.doi.org/10.18632/oncotarget.2756
    https://ir.csmu.edu.tw:8080/ir/handle/310902500/19277
    關聯: Oncotarget. 2015 Jan 30;6(3):1478-89
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