GPR55-Mediated Effects in Colon Cancer Cell Lines

The cannabinoid-responsive G protein-coupled receptor GPR55 and its endogenous ligand L-α-lysophosphatidylinositol (LPI) have been reported to play a role in several cancers. A proliferation-enhancing effect of GPR55 has been described for several cancer cell lines and LPI has been found elevated in cancer patients. The aim of this study was to investigate whether GPR55 signaling had an effect on the proliferation of colon cancer cell lines. Using cell viability assays and Western blotting, we show that stable overexpression of the GPR55 receptor led to a growth advantage of SW480 cells per se. Proliferation of native colon cancer cell lines, however, was not affected by pharmacological manipulation of GPR55. Interestingly though, GPR55 signaling was responsive to treatment with both the GPR55 agonist LPI and the antagonist CID16020046 in the overexpressing cancer cell lines. This was evident through significantly increased or decreased levels of phosphorylated ERK1/2, respectively. Taken together, our findings suggest that GPR55 is constitutively activated in overexpressing colon cancer cells affecting ERK1/2 phosphorylation and cell proliferation.

[1]  O. Sansom,et al.  GPR55 signalling promotes proliferation of pancreatic cancer cells and tumour growth in mice, and its inhibition increases effects of gemcitabine , 2018, Oncogene.

[2]  G. Muccioli,et al.  Lysophosphatidylinositols, from Cell Membrane Constituents to GPR55 Ligands. , 2018, Trends in pharmacological sciences.

[3]  S. Beck,et al.  G protein‐coupled receptor GPR55 promotes colorectal cancer and has opposing effects to cannabinoid receptor 1 , 2018, International journal of cancer.

[4]  J. Haybaeck,et al.  GPR55 promotes migration and adhesion of colon cancer cells indicating a role in metastasis , 2016, British journal of pharmacology.

[5]  M. Falasca,et al.  Role of the lysophosphatidylinositol/GPR55 axis in cancer. , 2016, Advances in biological regulation.

[6]  J. Flores,et al.  The orphan receptor GPR55 drives skin carcinogenesis and is upregulated in human squamous cell carcinomas , 2013, Oncogene.

[7]  M. Waldhoer,et al.  The Cannabinoid Receptor CB1 Modulates the Signaling Properties of the Lysophosphatidylinositol Receptor GPR55* , 2012, The Journal of Biological Chemistry.

[8]  C. Henstridge.  Off-Target Cannabinoid Effects Mediated by GPR55 , 2012, Pharmacology.

[9]  J. Gertsch,et al.  Endocannabinoid content in fetal bovine sera - unexpected effects on mononuclear cells and osteoclastogenesis. , 2011, Journal of immunological methods.

[10]  R. Piñeiro,et al.  The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation , 2011, Oncogene.

[11]  G. Velasco,et al.  The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK , 2011, Oncogene.

[12]  M. Caron,et al.  Identification of the GPR55 agonist binding site using a novel set of high-potency GPR55 selective ligands. , 2011, Biochemistry.

[13]  A. Irving,et al.  The GPR55 ligand L‐α‐lysophosphatidylinositol promotes RhoA‐dependent Ca2+ signaling and NFAT activation , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  A. Yamashita,et al.  2-Arachidonoyl-sn-glycero-3-phosphoinositol: a possible natural ligand for GPR55. , 2008, Journal of biochemistry.

[15]  K. Mackie,et al.  GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current , 2008, Proceedings of the National Academy of Sciences.

[16]  S. Hjorth,et al.  The orphan receptor GPR55 is a novel cannabinoid receptor , 2007, British journal of pharmacology.

[17]  A. Yamashita,et al.  Identification of GPR55 as a lysophosphatidylinositol receptor. , 2007, Biochemical and biophysical research communications.

[18]  B. Olde,et al.  Lysophosphatidic Acid Binds to and Activates GPR92, a G Protein-Coupled Receptor Highly Expressed in Gastrointestinal Lymphocytes , 2006, Journal of Pharmacology and Experimental Therapeutics.

[19]  M. Glass,et al.  Evolutionary origins of the endocannabinoid system. , 2006, Gene.

[20]  Takao Shimizu,et al.  Identification of p2y9/GPR23 as a Novel G Protein-coupled Receptor for Lysophosphatidic Acid, Structurally Distant from the Edg Family* , 2003, Journal of Biological Chemistry.