Journal article

CSK-homologous kinase (CHK/MATK) is a potential colorectal cancer tumour suppressor gene epigenetically silenced by promoter methylation

Anderly C Chueh, Gahana Advani, Momeneh Foroutan, Jai Smith, Nadia Ng, Harshal Nandurkar, Daisy S Lio, Hong-Jian Zhu, Yuh-Ping Chong, Heather Verkade, Donald J Fujita, Jeffrey Bjorge, Faiza Basheer, Jet Phey Lim, Ian Luk, Amardeep Dhillon, Anuratha Sakthianandeswaren, Dmitri Mouradov, Oliver Sieber, Frederic Hollande Show all



Hyperactivation of SRC-family protein kinases (SFKs) contributes to the initiation and progression of human colorectal cancer (CRC). Since oncogenic mutations of SFK genes are rare in human CRC, we investigated if SFK hyperactivation is linked to dysregulation of their upstream inhibitors, C-terminal SRC kinase (CSK) and its homolog CSK-homologous kinase (CHK/MATK). We demonstrate that expression of CHK/MATK but not CSK was significantly downregulated in CRC cell lines and primary tumours compared to normal colonic tissue. Investigation of the mechanism by which CHK/MATK expression is down-regulated in CRC cells uncovered hypermethylation of the CHK/MATK promoter in CRC cell lines and primar..

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Awarded by NHMRC

Awarded by Australian Brain Foundation

Awarded by NHMRC Senior Research fellowship

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

O. Sieber is a NHMRC Senior Research Fellow (GNT1136119); grant support to H.-J. Zhu: NHMRC project grant #628727, grant support to H.-C. Cheng: NHMRC project grant # 1050486 and Australian Brain Foundation, grant support to A. Dhillon: NHMRC project grants #1141906. J. Mariadason was supported by a NHMRC Senior Research fellowship (GNT1046092). F. Hollande received grants from the Tour de Cure Foundation, Australia (Senior Project grant) and the National Health and Medical Research Council of Australia (Grant #1164081).