CDK5 is essential for TGF-β1-induced epithelial-mesenchymal transition and breast cancer progression

• DOI: 10.1038/srep02932
• Publication Date: 2013-10-14T09:10:43Z
• Authors: Qian Liang; Lili Li; Jianchao Zhang; Yang Lei; Liping Wang; Dong-Xu Liu; Jingxin Feng; Pingfu Hou; Ruosi Yao; Yu Zhang; Baiqu Huang; Jun Lu
• Keywords: 0303 health sciences; Epithelial-Mesenchymal Transition; Gene Expression; Breast Neoplasms; Cyclin-Dependent Kinase 5; Nerve Tissue Proteins; Article; Actins; 3. Good health; Enzyme Activation; Transforming Growth Factor beta1; 03 medical and health sciences; Cell Transformation, Neoplastic; Cell Movement; Cell Line, Tumor; Focal Adhesion Protein-Tyrosine Kinases; Gene Knockdown Techniques; Disease Progression; Humans; Female; Neoplasm Grading; Phosphorylation

Epithelial-mesenchymal transition is a change of cellular plasticity critical for embryonic development and tumor metastasis. CDK5 is a proline-directed serine/threonine kinase playing important roles in cancer progression. Here we show that CDK5 is commonly overexpressed and significantly correlated with several poor prognostic parameters of breast cancer. We found that CDK5 participated in TGF-β1-induced EMT. In MCF10A, TGF-β1 upregulated the CDK5 and p35 expression, and CDK5 knockdown inhibited TGF-β1-induced EMT. CDK5 overexpression also exhibited a potential synergy in promoting TGF-β1-induced EMT. In mesenchymal breast cancer cells MDA-MB-231 and BT549, CDK5 knockdown suppressed cell motility and tumorigenesis. We further demonstrated that CDK5 modulated cancer cell migration and tumor formation by regulating the phosphorylation of FAK at Ser-732. Therefore, CDK5-FAK pathway, as a downstream step of TGF-β1 signaling, is essential for EMT and motility in breast cancer cells. This study implicates the potential value of CDK5 as a molecular marker for breast cancer.