Inactivation of the kinase domain of CDK10 prevents tumor growth in a preclinical model of colorectal cancer, and is accompanied by downregulation of Bcl-2

Cyclin dependent kinase 10 (CDK10), a CDC2 related kinase, is highly expressed in colorectal cancer (CRC). Its role in the pathogenesis of CRC is unknown. This study examines the function of CDK10 in CRC, and demonstrates its role in suppressing apoptosis and in promoting tumor growth in vitro and in vivo. Modulation of CDK10 expression in CRC cell lines demonstrates that CDK10 promotes cell growth, reduces chemosensitivity and inhibits apoptosis by upregulating the expression of Bcl-2. This effect appears to depend on its kinase activity, as kinase-defective mutant CRC cell lines have an exaggerated apoptotic response and reduced proliferative capacity. In vivo, inhibiting CDK10 in CRC following intratumoral injections of lentivirus-mediated CDK10 siRNA in a patient-derived xenograft mouse model demonstrated its efficacy in suppressing tumor growth. Furthermore, using a tissue microarray of human CRC tissues, the potential for CDK10 to be a prognostic biomarker in CRC was explored. In tumors of individuals with CRC, high expression of CDK10 correlates with earlier relapse and shorter overall survival. The findings of this study indicate that CDK10 plays a role in the pathogenesis in CRC and may be a potential therapeutic target for treatment.

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