Caldesmon Phosphorylation Plays a Key Role in Tumor Metastasis

• 1、Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016
• 2、(Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016

Abstract：In this paper, we have performed transwell migration assays and contractility measurements by traction microscopy using human breast cancer cell lines MDA MB-231 and MCF-7, transfected with wild-type or mutated CaD. We found that cells expressing the A1234 mutant of CaD exhibited most robust contractile activity, the effect being more profound in MDA-MB231 cells than in MCF-7 cells, whereas the same mutant resulted in most severely hampered migration in both types of cells. These mutant cells also exhibited enhanced stress fibers and delayed trypsin-induced detachment from substratum. Taken together, phosphorylation of CaD appears to have an opposite effect on cell migration and contractility. Cells with extensive and dynamic CaD phosphorylation favor motile activities. Unphosphorylated CaD facilitates stable actin filaments, which is needed to support cell contractility, but could stifle cell movement if irreversible. The observed difference between the two tumor cell lines may thus reflect their different intrinsic kinase activities. The metastatic MDA-MB231 cells have higher levels of CaD and more active kinases than the non-metastatic MCF-7 cells. An elevated amount of phosphorylated CaD contributes to cell migration and invasion. Our findings not only shed light on the mechanism by which CaD regulates cell motility, but also provide new insights into the nature of metastasis of cancer cells.

keywords： Caldesmon Phosphorylation Metastasis

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