ASIA unversity:Item 310904400/108230
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    题名: Targeting the VEGF-C/VEGFR3 axis suppresses Slug-mediated cancer metastasis and stemness via inhibition of KRAS/YAP1 signaling.
    作者: CP；余永倫；蘇振良；；, Yeh YW；Yeh YW；Cheng CC；Cheng CC；Yang ST；Yang ST；Tseng CF；Tseng CF；Chang TY；Chang TY；Tsai SY；Tsai SY；Fu E；Fu E；Chiang CP；Chiang
    贡献者: 生物科技學系
    日期: 2017-01
    上传时间: 2017-10-30 02:44:53 (UTC+0)
    摘要: Vascular endothelial growth factor-C (VEGF-C) has been implicated in epithelial-mesenchymal transition (EMT) processes and various human cancers, including skin cancer. Skin cancer is an aggressive human malignancy with increasing incidence worldwide; however, the underlying mechanisms involved in VEGF-C-induced skin cancer stemness and metastasis remain unclear. Here, we report that VEGF-C enhances skin cancer migration, invasion and stemness through Slug up-regulation. Oncomine database analysis indicated that the KRAS/MAPK (mitogen-activated protein kinases) pathway and YAP1 (yes-associated protein 1) expression are positively correlated with metastatic skin cancer. We show that VEGF-C triggers the activation of KRAS/MAPK signaling to increase YAP1 and downstream Slug expression, which are suppressed by an anti-VEGFR3 (VEGF receptor 3) peptide, a specific peptide targeting VEGFR3. The VEGF-C-induced migration, invasion and stemness of skin cancer cells are also abrogated by the anti-VEGFR3 peptide. Based on these data, we reveal the role of the VEGF-C/VEGFR3-mediated KRAS/MAPK-YAP1/Slug pathway in skin cancer progression and propose that the VEGF-C/VEGFR3 axis is a promising target for the anti-VEGFR3 peptide.

    KEYWORDS:
    VEGF-C; YAP1; cancer stemness; metastasis; skin cancer
    關聯: Oncotarget
    显示于类别:[生物科技學系] 期刊論文

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