Figure S3 from 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

https://doi.org/10.1158/1535-7163.22508854

figure

posted on 2023-04-03, 15:50 authored by Louis-Bastien Weiswald, Mohammad R. Hasan, John C.T. Wong, Clarissa C. Pasiliao, Mahbuba Rahman, Jianhua Ren, Yaling Yin, Samuel Gusscott, Sophie Vacher, Andrew P. Weng, Hagen F. Kennecke, Ivan Bièche, David F. Schaeffer, Donald T. Yapp, Isabella T. Tai

<p>Effect of CDK10 expression on cell proliferation and apoptosis in vivo. Immunostaining of CDK10 WT and DN overexpressing MIP101 xenografts for Ki-67 (upper panel, red) and cleaved caspase-3 (lower panel, red) and counterstained with Hoechst 33258 (blue).</p>

Funding

Canadian Institutes of Health Research

France Canada Research Funds

History

Related Materials

1.
DOI - Is supplement to 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

ARTICLE ABSTRACT

Cyclin-dependent kinase 10 (CDK10), a CDC2-related kinase, is highly expressed in colorectal cancer. Its role in the pathogenesis of colorectal cancer is unknown. This study examines the function of CDK10 in colorectal cancer, and demonstrates its role in suppressing apoptosis and in promoting tumor growth in vitro and in vivo. Modulation of CDK10 expression in colorectal cancer 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 colorectal cancer cell lines have an exaggerated apoptotic response and reduced proliferative capacity. In vivo, inhibiting CDK10 in colorectal cancer 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 colorectal cancer tissues, the potential for CDK10 to be a prognostic biomarker in colorectal cancer was explored. In tumors of individuals with colorectal cancer, 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 colorectal cancer and may be a potential therapeutic target for treatment. Mol Cancer Ther; 16(10); 2292–303. ©2017 AACR.