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GPR78 promotes lung cancer cell migration and metastasis by activation of Gメq-Rho GTPase Pathway
Dan-Dan Dong1, Hui Zhou2, Gao Li3,*
1Department of Pathology, Sichuan Academy of Medical Sciences,
2Department of Thoracic Medicine, The Affiliated Cancer Hospital of Xiangya School of Medicine,
3Thoracic surgery, Hainan General Hospital
Abstract
GPR78 is an orphan G-protein coupled receptor (GPCR) that is predominantly expressed in human brain tissues. Currently, the function of GPR78 is unknown. In this study, we found that GPR78 was expressed in lung cancer cells and functioned as a novel regulator of lung cancer cell migration and metastasis. We found that knockdown of GPR78 in lung cancer cells suppressed cell migration. Moreover, GPR78 modulated the formation of actin stress fibers in A549 cells in a RhoA- and Rac1-dependent manner. At a molecular level, GPR78 regulated cell motility through the activation of Gメq-RhoA/Rac1 pathway. We further demonstrated that knockdown of GPR78 inhibited lung cancer cell metastasis in vivo. These findings suggest that GPR78 is a novel regulator for lung cancer metastasis and may serve as a potential drug target against metastatic human lung cancer.
Abstract, Accepted Manuscript(in press) [Submitted on August 4, 2016, Accepted on September 23, 2016]
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