title: GPR56 Regulates VEGF production and angiogenesis during melanoma progression.
abstract: Angiogenesis is a critical step during cancer progression. The VEGF is a major stimulator for angiogenesis and is predominantly contributed by cancer cells in tumors. Inhibition of the VEGF signaling pathway has shown promising therapeutic benefits for cancer patients, but adaptive tumor responses are often observed, indicating the need for further understanding of VEGF regulation. We report that a novel G protein-coupled receptor, GPR56, inhibits VEGF production from the melanoma cell lines and impedes melanoma angiogenesis and growth, through the serine threonine proline-rich segment in its N-terminus and a signaling pathway involving protein kinase Cα. We also present evidence that the two fragments of GPR56, which are generated by autocatalyzed cleavage, played distinct roles in regulating VEGF production and melanoma progression. Finally, consistent with its suppressive roles in melanoma progression, the expression levels of GPR56 are inversely correlated with the malignancy of melanomas in human subjects. We propose that components of the GPR56-mediated signaling pathway may serve as new targets for antiangiogenic treatment of melanoma.
authors: Departments of Biomedical Genetics, University of Rochester Medical Center, Rochester, New York 14612, USA.
authors: Liquan
authors: L
authors: Yang
authors: Guangchun
authors: G
authors: Chen
authors: Sonali
authors: S
authors: Mohanty
authors: Glynis
authors: G
authors: Scott
authors: Fabeha
authors: F
authors: Fazal
authors: Arshad
authors: A
authors: Rahman
authors: Shahinoor
authors: S
authors: Begum
authors: Richard O
authors: RO
authors: Hynes
authors: Lei
authors: L
authors: Xu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008545:Melanoma / Q000098:blood supply / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: C118925:ADGRG1 protein, human; D043562:Receptors, G-Protein-Coupled; D042461:Vascular Endothelial Growth Factor A