Csk-homologous kinase (Chk/Matk): a molecular policeman suppressing cancer formation and progression
- Author(s)
- Advani, G; Chueh, AC; Lim, YC; Dhillon, A; Cheng, HC;
- Details
- Publication Year 2015,Volume 10,Issue #3,Page 195-202
- Journal Title
- Front Biol
- Publication Type
- Journal Article
- Abstract
- Aberrant activation of Src-family tyrosine kinases (SFKs) directs initiation of metastasis and development of drug resistance in multiple solid tumors and hematological cancers. Since oncogenic mutations of SFKs are rare events, aberrant activation of SFKs in cancer is likely due to dysregulation of the two major upstream inhibitors: C-terminal Src kinase (Csk) and its homolog Csk-homologous kinase (Chk/Matk). Csk and Chk/Matk inhibit SFKs by selectively phosphorylating the inhibitory tyrosine residue at their C-terminal tail. Additionally, Chk/Matk can also employ a noncatalytic inhibitory mechanism to inhibit multiple active forms of SFKs, suggesting that Chk/Matk is a versatile inhibitor capable of constraining the activity of multiple active forms of SFKs. Mounting evidence suggests that Chk/Matk is a potential tumor suppressor downregulated by epigenetic silencing and/or missense mutations in several cancers such as colorectal and lung carcinoma. In spite of the potential significance of Chk/Matk in cancer, little is known about its structure and regulation. This review focuses on the mechanisms by which Chk/Matk expression and activity is downregulated in cancers. Specifically, we assessed the evidence demonstrating downregulation of Chk/Matk by epigenetic silencing and missense mutations in cancers. The other focus is the tumor suppressive mechanism of Chk/Matk. The final focus of the review is on the clinical applications of the investigations into the mechanism of epigenetic silencing of Chk/Matk expression and the tumor suppressive mechanism of Chk/Matk; specifically we discussed how they can benefit the development of biomarkers for early diagnosis of cancers and specific SFK inhibitors for use as cancer therapeutics. © 2015, Higher Education Press and Springer-Verlag Berlin Heidelberg.
- Publisher
- Springer
- Keywords
- CHK/Matk; colon cancer; CSK; protein tyrosine kinase; Src-family kinases; tumour suppressor
- Research Division(s)
- Chemical Biology
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-10-28 03:35:34
Last Modified: 2015-11-19 10:33:19