Role of gamma-synuclein in microtubule regulation |
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Authors: | Zhang Hong Kouadio Ange Cartledge Donna Godwin Andrew K |
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Institution: | aWomen's Cancer Program, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA;bAndrews University, Berrien Springs, MI 49104, USA;cDepartment of Biomedical Research, Alfred I duPont Hospital for Children, Wilmington, DE 19803, USA;dDepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA |
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Abstract: | Gamma-synuclein is a neuronal protein found in peripheral and motor nerve systems. It becomes highly expressed in metastatic but not in primary tumor or normal tissues. The close association between gamma-synuclein expression and cancer spreading has been demonstrated in a broad range of malignancies. Our previous study showed that exogenous expression of gamma-synuclein in ovarian and breast cancer cells significantly enhanced cell migration and resistance to paclitaxel-induced apoptotic death. In our current research, we found that gamma-synuclein can affect microtubule properties and act as a functional microtubule associated protein. In vitro assays revealed that gamma-synuclein can bind and promote tubulin polymerization, induce the microtubule bundling and alter microtubule morphology developed in the presence of microtubule associated protein 2 (MAP2). Using cancer cell lysate, gamma-synuclein protein was found to be localized in both cytosolic compartment and extracted cytoskeleton portion. Immunofluorescence staining demonstrated that gamma-synuclein can colocalize with microtubule in HeLa cells and decrease rigidity of microtubule bundles caused by paclitaxel. In human ovarian cancer epithelial A2780 cells, gamma-synuclein overexpression improved cell adhesion and microtubule structure upon paclitaxel treatment. Importantly, it led to microtubule-dependent mitochondria clustering at perinuclear area. These observations suggest that overexpression of gamma-synuclein may reduce cell chemo-sensitivity of tumor cells through decreasing microtubule rigidity. In summary, our studies suggested that gamma-synuclein can directly participate in microtubule regulation. |
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Keywords: | Gamma-synuclein Cancer Drug resistance Paclitaxel Microtubule |
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