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G-protein coupled receptor 64 (GPR64) acts as a tumor suppressor in endometrial cancer

 Jong Il Ahn  ;  Jung-Yoon Yoo  ;  Tae Hoon Kim  ;  Young Im Kim  ;  Russell R Broaddus  ;  Ji Yeon Ahn  ;  Jeong Mook Lim  ;  Jae-Wook Jeong 
 BMC CANCER, Vol.19(1) : 810, 2019-08 
Journal Title
Issue Date
AMP-Activated Protein Kinases / metabolism ; Carcinoma, Endometrioid / genetics ; Carcinoma, Endometrioid / metabolism ; Carcinoma, Endometrioid / pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Connexin 43 / metabolism ; Endometrial Neoplasms / genetics ; Endometrial Neoplasms / metabolism ; Endometrial Neoplasms / pathology* ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Invasiveness ; Phosphorylation ; RNA, Small Interfering ; Receptors, G-Protein-Coupled / antagonists & inhibitors ; Receptors, G-Protein-Coupled / genetics ; Receptors, G-Protein-Coupled / metabolism*
Endometrial cancer ; Tumor suppressor ; GPR64 ; Connexin 43
Background Endometrial cancer is the most common gynecological cancer. G-protein coupled receptor 64 (GPR64) belongs to a family of adhesion GPCRs and plays an important role in male fertility. However, the function of GPR64 has not been studied in endometrial cancer. Our objective is to investigate the role of GPR64 in endometrial cancer. Methods We examined the levels of GPR64 in human endometrioid endometrial carcinoma by immunohistochemistry analysis. To determine a tumor suppressor role of GPR64 in endometrial cancer, we used a siRNA loss of function approach in human endometrial adenocarcinoma cell lines. Results GPR64 levels were remarkably lower in 10 of 21 (47.62%) of endometrial carcinoma samples compared to control. Depletion of GPR64 by siRNA transfection revealed an increase of colony formation ability, cell proliferation, cell migration, and invasion activity in Ishikawa and HEC1A cells. The expression of Connexin 43 (Cx43), a member of the large family of gap junction proteins, was reduced through activation of AMP-activated protein kinase (AMPK) in Ishikawa cells with GPR64-deficicy. Conclusions These results suggest that GPR64 plays an important tumor suppressor role in endometrial cancer.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Yoo, Jung Yoon(유정윤) ORCID logo https://orcid.org/0000-0001-9366-3863
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