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dc.contributor.authorSie, Zong-Linen_US
dc.contributor.authorLi, Ruei-Yangen_US
dc.contributor.authorSampurna, Bonifasius Puteraen_US
dc.contributor.authorHsu, Po-Juien_US
dc.contributor.authorLiu, Shu-Chenen_US
dc.contributor.authorWang, Horng-Daren_US
dc.contributor.authorHuang, Chou-Longen_US
dc.contributor.authorYuh, Chiou-Hwaen_US
dc.date.accessioned2020-07-01T05:22:11Z-
dc.date.available2020-07-01T05:22:11Z-
dc.date.issued2020-03-01en_US
dc.identifier.urihttp://dx.doi.org/10.3390/cancers12030575en_US
dc.identifier.urihttp://hdl.handle.net/11536/154597-
dc.description.abstractWith-no-lysine (K)-1 (WNK1) is the founding member of family of four protein kinases with atypical placement of catalytic lysine that play important roles in regulating epithelial ion transport. Gain-of-function mutations of WNK1 and WNK4 cause a mendelian hypertension and hyperkalemic disease. WNK1is ubiquitously expressed and essential for embryonic angiogenesis in mice. Increasing evidence indicates the role of WNK kinases in tumorigenesis at least partly by stimulating tumor cell proliferation. Here, we show that human hepatoma cells xenotransplanted into zebrafish produced high levels of vascular endothelial growth factor (VEGF) and WNK1, and induced expression of zebrafish wnk1. Knockdown of wnk1 in zebrafish decreased tumor-induced ectopic vessel formation and inhibited tumor proliferation. Inhibition of WNK1 or its downstream kinases OSR1 (oxidative stress responsive kinase 1)/SPAK (Ste20-related proline alanine rich kinase) using chemical inhibitors decreased ectopic vessel formation as well as proliferation of xenotransplanted hepatoma cells. The effect of WNK and OSR1 inhibitors is greater than that achieved by inhibitor of VEGF signaling cascade. These inhibitors also effectively inhibited tumorigenesis in two separate transgenic zebrafish models of intestinal and hepatocellular carcinomas. Endothelial-specific overexpression of wnk1 enhanced tumorigenesis in transgenic carcinogenic fish, supporting endothelial cell-autonomous effect of WNK1 in tumor promotion. Thus, WNK1 can promote tumorigenesis by multiple effects that include stimulating tumor angiogenesis. Inhibition of WNK1 may be a potent anti-cancer therapy.en_US
dc.language.isoen_USen_US
dc.subjectwith-no-lysine (K) kinase Ien_US
dc.subjecttumor-induced angiogenesisen_US
dc.subjectzebrafishen_US
dc.subjecthepatocellular carcinomaen_US
dc.subjectcolorectal canceren_US
dc.titleWNK1 Kinase Stimulates Angiogenesis to Promote Tumor Growth and Metastasisen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/cancers12030575en_US
dc.identifier.journalCANCERSen_US
dc.citation.volume12en_US
dc.citation.issue3en_US
dc.citation.spage0en_US
dc.citation.epage0en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.identifier.wosnumberWOS:000530232300051en_US
dc.citation.woscount1en_US
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