Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

The putative cannabinoid receptor GPR55 promotes cancer cell proliferation

Abstract

Cannabinoids, the active ingredients in marijuana, have dramatic effects on various organ systems. They exert their effects through two receptor types: CB1, primarily located in the brain, and CB2, primarily located in the immune system. Vertebrates also produce their own cannabinoid-like substances called endocannabinoids, including anandamide and 2-arachidonoylglyceral. Interestingly, some effects of endocannabinoids could not be explained by the signals through either CB1 or CB2. Recently, the orphan G protein-coupled receptor 55 (GPR55) was proposed to be an atypical cannabinoid receptor. In this issue of Oncogene, two groups demonstrated that GPR55 is expressed in various cancer types in an aggressiveness-related manner, suggesting a novel cancer biomarker and a potential therapeutic target.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

References

  • Alexander A, Smith PF, Rosengren RJ . (2009). Cannabinoids in the treatment of cancer. Cancer Lett 285: 6–12.

    Article  CAS  Google Scholar 

  • Andradas C, Caffarel MM, Pérez-Gómez E, Salazar M, Lorente M, Velasco G et al. (2010). The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK. Oncogene (e-pub ahead of print 6 September 2010; doi:10.1038/onc.2010.402).

    Article  Google Scholar 

  • Das SK, Paria BC, Chakraborty I, Dey SK . (1995). Cannabinoid ligand-receptor signaling in the mouse uterus. Proc Natl Acad Sci USA 92: 4332–4336.

    Article  CAS  Google Scholar 

  • Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G et al. (1992). Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258: 1946–1949.

    Article  CAS  Google Scholar 

  • Ford LA, Roelofs AJ, Anavi-Goffer S, Mowat L, Simpson DG, Irving AJ et al. (2010). A role for L-alpha-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells. Br J Pharmacol 160: 762–771.

    Article  CAS  Google Scholar 

  • Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K . (2008). GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci USA 105: 2699–2704.

    Article  CAS  Google Scholar 

  • Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR et al. (1995). Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50: 83–90.

    Article  CAS  Google Scholar 

  • Oesch S, Gertsch J . (2009). Cannabinoid receptor ligands as potential anticancer agents--high hopes for new therapies? J Pharm Pharmacol 61: 839–853.

    CAS  PubMed  Google Scholar 

  • Oka S, Kimura S, Toshida T, Ota R, Yamashita A, Sugiura T . (2010). Lysophosphatidylinositol induces rapid phosphorylation of p38 mitogen-activated protein kinase and activating transcription factor 2 in HEK293 cells expressing GPR55 and IM-9 lymphoblastoid cells. J Biochem 147: 671–678.

    Article  CAS  Google Scholar 

  • Piñeiro R, Maffucci T, Falasca M . (2010). The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation. Oncogene (e-pub ahead of print 13 September 2010; doi:10.1038/onc.2010.417).

    Article  Google Scholar 

  • Sharir H, Abood ME . (2010). Pharmacological characterization of GPR55, a putative cannabinoid receptor. Pharmacol Ther 126: 301–313.

    Article  CAS  Google Scholar 

  • Staton PC, Hatcher JP, Walker DJ, Morrison AD, Shapland EM, Hughes JP et al. (2008). The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. Pain 139: 225–236.

    Article  CAS  Google Scholar 

  • Sugiura T, Kodaka T, Kondo S, Tonegawa T, Nakane S, Kishimoto S et al. (1996). 2-Arachidonoylglycerol, a putative endogenous cannabinoid receptor ligand, induces rapid, transient elevation of intracellular free Ca2+ in neuroblastoma x glioma hybrid NG108-15 cells. Biochem Biophys Res Commun 229: 58–64.

    Article  CAS  Google Scholar 

  • Whyte LS, Ryberg E, Sims NA, Ridge SA, Mackie K, Greasley PJ et al. (2009). The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proc Natl Acad Sci USA 106: 16511–16516.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Y Shi.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hu, G., Ren, G. & Shi, Y. The putative cannabinoid receptor GPR55 promotes cancer cell proliferation. Oncogene 30, 139–141 (2011). https://doi.org/10.1038/onc.2010.502

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2010.502

This article is cited by

Search

Quick links