Function And Mechanism Analysis Of Gpr55 In Mice Colorectal Cancer Tumorigenesis

G protein-coupled receptors (GPCRs) constitute by far the largest cell membrane receptor family in mammals and are involved in the regulation of virtually all cellular and physiological functions in the body, such as cell proliferation, differentiation and migration. GPCRs are involved in many disease progressions and are preferentially targeted for the development of new therapeutics. The functions of most GPCRs are unknown. Thus to study the function of GPCRs is of most importance for unveiling the mechanism of diseases and discovering novel drug targets.The orphan G protein-coupled receptor GPR55, which is activated by 1-lysophosphatidylinositol and interacts with cannabinoid (CB) receptor ligands, has been proposed as putative cannabinoid receptor. The function of Gpr55 is very broadly, giving the receptor an important role in body development and tumorigenesis in mice. So far, Gpr55 has been proposed as a new potential drug target for the treatment of diabetes, obesity and cancer. However, the roles of Gpr55 in the inflammatory bowel disease and colorectal cancer are not clear. So we generated Gpr55 Knockout mice by TALEN, a new gene knockout technology. We found that there’s no obvious difference in the phenotype between WT and KO mice after DSS-induced inflammation. However Gpr55-deficient mice are more resistant to AOM/DSS induced inflammation-related colon cancer. The tumor number and size in WT mice are bigger than Gpr55-deficient mice, suggesting deletion of Gpr55 may have an impact on colon tumorgenesis. To further explore the mechanism of this phenomenon, Immunohistochemical Staining and Western Blot were used to detect cell proliferation of tumor tissues and the expression of ERK signaling pathway related proteins respectively. Our results show that the cell proliferation and expression of p-ERK proteins were significantly higher in WT mice than those in Gpr55 knockout mice. Therefore, the orphan G protein-coupled receptor GPR55 may promote colorectal cancer proliferation via ERK signaling pathway.