title: CDK5 is essential for TGF-β1-induced epithelial-mesenchymal transition and breast cancer progression.
abstract: 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.
authors.affiliation: 1] The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Auckland, New Zealand [2].
authors.forename: Qian
authors.initials: Q
authors.lastname: Liang
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Jianchao
authors.initials: J
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Lei
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Liu
authors.forename: Jingxin
authors.initials: J
authors.lastname: Feng
authors.forename: Pingfu
authors.initials: P
authors.lastname: Hou
authors.forename: Ruosi
authors.initials: R
authors.lastname: Yao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Baiqu
authors.initials: B
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
mesh_terms: D000199:Actins / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics* / Q000378:metabolism*; D018450:Disease Progression; D004789:Enzyme Activation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D060787:Neoplasm Grading; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D000199:Actins; D009419:Nerve Tissue Proteins; D053773:Transforming Growth Factor beta1; C089495:neuronal Cdk5 activator (p25-p35); D051416:Focal Adhesion Protein-Tyrosine Kinases; D051360:Cyclin-Dependent Kinase 5