Cancers, Vol. 12, Pages 575: WNK1 Kinase Stimulates Angiogenesis to Promote Tumor Growth and Metastasis

Cancers, Vol. 12, Pages 575: WNK1 Kinase Stimulates Angiogenesis to Promote Tumor Growth and Metastasis Cancers doi: 10.3390/cancers12030575 Authors: Zong-Lin Sie Ruei-Yang Li Bonifasius Putera Sampurna Po-Jui Hsu Shu-Chen Liu Horng-Dar Wang Chou-Long Huang Chiou-Hwa Yuh With-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. WNK1 is 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 effect...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research