Cyclin-dependent Kinase 4 In Breast Cancer Cell Invasion And Metastasis

Cyclin-dependent kinase 4(Cdk4) is a member of serine/threonine kinase family, which form complexs with various Cyclin D,functioning in promoting the progress of G1 phase.Many studies have shown that Cdk4 plays an important role in cancer proliferation and growth.However,the interaction correlation of Cdk4 and cancer cell metastasis,as well as the mechanism underlying are still not clear.Thus,I used breast cancer cell lines as models to explore the role of Cdk4 plays in cancer cell metastasis.By using ShRNA-mediated Cdk4 depletion and Cdk4 overexpression,I established Cdk4-suppressed cell and Cdk4-overexpressed breast cancer cell lines respectively.Through in vitro wound-healing assay and transwell assay,we found that suppressing Cdk4 led to reduction in invasion and metastasis of the breast cancer cells. In contrast,the EMT6 and MDA-MD-231 cancer cells with Cdk4 overexpression had significantly accerated invasion and metastasis.The further metastasis assay by mouse model in vivo also confirmed these same results,which suggest Cdk4 plays an important role in invasion and metastasis of breast cancer cells.In order to explore the mechanism of Cdk4 in the process of invasion and metastasis,I used microarray technology and Real-time PCR approach to check the expression change of the factors related to cell invasion and metastasis upon Cdk4-suppression and overexpression.The results showed that Cdk4 positively regulated the expression of these metastasis-related factors(e.g CXCL1,COX2,MMP1 et al) in the breast cancer cell lines.Thus,I hypothesized that Cdk4 control the invasion and metastasis of breast cancer cells through positively regulating the expression of the invasion/metastasis-associated factors.In summary,the present studies demonstrated the role of Cdk4 plays in invasion and metastasis of breast cancer cells,and reavealed the potential metastasis-related factors in breast cancer cells that correlated with Cdk4.These findings would provide a new insight and theoretical basis for the treatment of invasion breast cancer by targeting Cdk4.