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 Gαq-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. [BMB Reports 2016; 49(11): 623-628].
MeSH terms
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A549 Cells
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Animals
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Blotting, Western
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Cell Movement
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Endoplasmic Reticulum Chaperone BiP
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Female
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GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism*
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Heat-Shock Proteins
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Humans
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Mice
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Mice, Nude
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Neoplasm Invasiveness
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RNA Interference
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RNA, Messenger / metabolism
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RNA, Small Interfering / metabolism
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Real-Time Polymerase Chain Reaction
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Receptors, G-Protein-Coupled / antagonists & inhibitors
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism*
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Transplantation, Heterologous
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rac1 GTP-Binding Protein / genetics
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rac1 GTP-Binding Protein / metabolism*
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rhoA GTP-Binding Protein / genetics
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rhoA GTP-Binding Protein / metabolism*
Substances
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Endoplasmic Reticulum Chaperone BiP
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GPR26 protein, human
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HSPA5 protein, human
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Heat-Shock Proteins
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Hspa5 protein, mouse
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RNA, Messenger
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RNA, Small Interfering
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Receptors, G-Protein-Coupled
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GTP-Binding Protein alpha Subunits, Gq-G11
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rac1 GTP-Binding Protein
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rhoA GTP-Binding Protein