GPR171 expression enhances proliferation and metastasis of lung cancer cells

// So Hee Dho 1, 2 , Kwang-Pyo Lee 1 , Dongjun Jeong 3 , Chang-Jin Kim 3 , Kyung-Sook Chung 4 , Ji Young Kim 1 , Bum-Chan Park 1 , Sung Sup Park 1 , Seon-Young Kim 4, 5 , Ki-Sun Kwon 1, 5 1 Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea 2 Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353, Republic of Korea 3 Department of Pathology, College of Medicine Soonchunhyang University, Chonan 330-090, Republic of Korea 4 Genome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea 5 Department of Functional Genomics, Korea University of Science and Technology (UST), Daejeon 305-333, Republic of Korea Correspondence to: Ki-Sun Kwon, e-mail: kwonks@kribb.re.kr Keywords: GPCR, GPR171, EGFR, lung cancer Received: August 03, 2015      Accepted: January 02, 2016      Published: January 09, 2016 ABSTRACT G protein-coupled receptors (GPCRs) are among the most significant therapeutic targets and some of them promote the growth and metastasis of cancer. Here, we show that an increase in the levels of GPR171 is crucial for lung cancer tumor progression in vitro and in vivo . Immunostaining of clinical samples indicated that GPR171 was overexpressed in 46.8% of lung carcinoma tissues. Depletion of GPR171 with an anti-GPR171 antibody decreased proliferation of lung carcinoma cells and attenuated tumor progression in a mouse xenograft model. Knockdown of GPR171 also inhibited migration and invasion of the lung cancer cell lines. Notably, inhibition of GPR171 synergistically enhanced the tumoricidal activity of an epidermal growth factor receptor (EGFR) inhibitor in lung cancer cells. These results indicate that GPR171 blockade is a promising antineoplastic strategy and provide a preclinical rationale for combined inhibition of GPR171 and EGFR.