An update regarding the role of WNK kinases in cancer

• Published in: Cell death & disease Vol. 13; no. 9; p. 795
• Main Authors: Xiu, Mengxi, Li, Li, Li, Yandong, Gao, Yong
• Format: Journal Article
• Language: English
• Published: England Springer Nature B.V 19.09.2022; Nature Publishing Group UK; Nature Publishing Group
• Subjects: Alanine; Angiogenesis; Animals; Autophagy; Bicarbonates; Binding sites; Blood pressure; Cancer; Cell adhesion & migration; Chloride; Chloride channels; Disease; Drug delivery; Homeostasis; Kinases; Liver cancer; Mammals; Medical prognosis; Metastases; Metastasis; Neoplasms - genetics; Neovascularization, Pathologic; Oxidative stress; Phosphorylation; Proline; Proteins; Review; Roles; Serine; Sodium; Sodium bicarbonate; Sodium channels; Sodium Chloride Symporters; Testicular cancer; Threonine; Tumors
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-022-05249-y

Mammalian WNK kinases (WNKs) are serine/threonine kinases that contain four members, WNK1-4. They function to maintain ion homeostasis and regulate blood pressure in mammals. Recent studies have revealed that the dysregulation of WNKs contributes to tumor growth, metastasis, and angiogenesis through complex mechanisms, especially through phosphorylating kinase substrates SPS1-related proline/alanine-rich kinase (SPAK) and oxidative stress-responsive kinase 1 (OSR1). Here, we review and discuss the relationships between WNKs and several key factors/biological processes in cancer, including ion channels, cation chloride cotransporters, sodium bicarbonate cotransporters, signaling pathways, angiogenesis, autophagy, and non-coding RNAs. In addition, the potential drugs for targeting WNK-SPAK/OSR1 signaling have also been discussed. This review summarizes and discusses knowledge of the roles of WNKs in cancer, which provides a comprehensive reference for future studies.