國家衛生研究院 NHRI:Item 3990099045/10192
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10192


    Title: Targeting the VEGF-C/VEGFR3 axis suppresses Slug-mediated cancer metastasis and stemness via inhibition of KRAS/YAP1 signaling
    Authors: Yeh, YW;Cheng, CC;Yang, ST;Tseng, CF;Chang, TY;Tsai, SY;Fu, E;Chiang, CP;Liao, LC;Tsai, PW;Yu, YL;Su, JL
    Contributors: National Institute of Cancer Research
    Abstract: 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.
    Date: 2017-01
    Relation: Oncotarget. 2017 Jan;8(3):5603-5618.
    Link to: http://dx.doi.org/10.18632/oncotarget.13629
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000393228400147
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85012014466
    Appears in Collections:[Jen-Liang Su] Periodical Articles

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