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GPR78 promotes lung cancer cell migration and metastasis by activation of Gαq-Rho GTPase pathway

  • Dong, Dan-Dan (Department of Pathology, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital) ;
  • Zhou, Hui (Department of Thoracic Medicine, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University) ;
  • Li, Gao (Thoracic Surgery, Hainan General Hospital)
  • Received : 2016.08.04
  • Accepted : 2016.09.23
  • Published : 2016.11.30

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. This study revealed 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 the molecular level, GPR78 regulated cell motility through the activation of $G{\alpha}q$-RhoA/Rac1 pathway. We further demonstrated that in vivo, the knockdown of GPR78 inhibited lung cancer cell metastasis. 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.

Keywords

GPR78;Lung cancer;Metastasis;Rho GTPase

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