Cancer Management and Research (Jan 2020)
Characterization of the Golgi scaffold protein PAQR3, and its role in tumor suppression and metabolic pathway compartmentalization
Abstract
Lan Lei, 1, 2 Zhe-Nan Ling, 3 Xiang-Liu Chen, 1 Lian-Lian Hong, 1 Zhi-Qiang Ling 1 1Department of Molecular Oncology, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Gongshu District, Hangzhou, 310022, People’s Republic of China; 2The Second Clinical Medical College of Zhejiang Chinese Medicine University, Hangzhou 310053, People’s Republic of China; 3Department of Clinical Medicine, Medical College, Zhejiang University City College, Hangzhou 310015, People’s Republic of ChinaCorrespondence: Zhi-Qiang LingDepartment of Molecular Oncology, Zhejiang Cancer Institute, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, No.1 Banshan East Road, Gongshu District, Hangzhou 310022, People’s Republic of ChinaEmail [email protected]: The Golgi apparatus is critical in the compartmentalization of signaling cascades originating from the cytoplasmic membrane and various organelles. Scaffold proteins, such as progestin and adipoQ receptor (PAQR)3, specifically regulate this process, and have recently been identified in the Golgi apparatus. PAQR3 belongs to the PAQR family, and was recently described as a tumor suppressor. Accumulating evidence demonstrates PAQR3 is downregulated in different cancers to suppress its inhibitory effects on malignant potential. PAQR3 functions biologically through the pathological regulation of altered signaling pathways. Significant cell proliferation networks, including Ras proto-oncogene (Ras)/mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), insulin, and vascular endothelial growth factor, are closely controlled by PAQR3 for physiologically relevant effects. Meanwhile, genetic/epigenetic susceptibility and environmental factors, may have functions in the downregulation of PAQR3 in human cancers. This study aimed to assess the subcellular localization of PAQR3 and determine its topological features and functional domains, summarizing its effects on cell signaling compartmentalization. The pathophysiological functions of PAQR3 in cancer pathogenesis, metabolic diseases, and developmental ailments were also highlighted.Keywords: cell signaling, Golgi apparatus, metabolic regulation, metastasis, PAQR3, tumor suppressor
