GPR56 Regulates VEGF Production and Angiogenesis during Melanoma Progression
Author(s)
Yang, Liquan; Chen, Guangchun; Mohanty, Sonali; Scott, Glynis; Fazal, Fabeha; Rahman, Arshad; Begum, Shahinoor; Hynes, Richard O; Xu, Lei,S.M.Massachusetts Institute of Technology.; ... Show more Show less
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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. Cancer Res; 71(16); 5558–68.
Description
2012 February 15
Date issued
2011-07Department
Massachusetts Institute of Technology. Department of Biology; Koch Institute for Integrative Cancer Research at MITJournal
Cancer Research
Publisher
American Association for Cancer Research
Citation
Yang, L. et al. “GPR56 Regulates VEGF Production and Angiogenesis During Melanoma Progression.” Cancer Research 71.16 (2011): 5558–5568.
Version: Author's final manuscript
ISSN
0008-5472
1538-7445