Dock4 forms a complex with SH3YL1 and regulates cancer cell migration |
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| Institution: | 1. Department of Polymer Science and Engineering, Hebei University of Technology, Tianjin 300130 PR China;2. DWELL Company Limited, Beijing 100083 PR China;1. Department of Medical Genetics, Medical School, University of Athens, Greece;2. First Department of Neurology, University of Athens Medical School, Athens, Greece;3. Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Aghia Sophia Children''s Hospital, Athens, Greece;4. Collaborative Center for Clinical Epidemiology and Outcomes Research (CLEO), 1st and 2nd Departments of Pediatrics, Aghia Sophia Children''s Hospital, Athens, Greece |
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| Abstract: | Dock4 is a member of the Dock180 family of proteins that mediates cancer cell migration through activation of Rac. However, the regulatory mechanism of Dock4 remains unclear. In this study, we show that the C-terminal proline-rich region of Dock4 is essential for the Dock4 mediated promotion of cell migration in MDA-MB-231 breast cancer cells. We found that a phosphoinositide-binding protein SH3YL1 interacted with the C-terminal proline-rich region of Dock4. Interaction of SH3YL1 with Dock4 promoted Dock4-mediated Rac1 activation and cell migration. Mutations in the phosphoinositide-binding domain disrupted the ability of SH3YL1 to promote Dock4-mediated cell migration. In addition, depletion of SH3YL1 in MDA-MB-231 cells suppressed cell migration. Taken together, these results provide evidence for a novel and functionally important interaction between Dock4 and SH3YL1 to promote cancer cell migration by regulating Rac1 activity. |
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