The orphan receptor GPR55 drives skin carcinogenesis and is upregulated in human squamous cell carcinomas

E Pérez-Gómez1, C Andradas, J M Flores

  • 1Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.

Oncogene
|July 4, 2012
PubMed

Insights

The orphan G protein-coupled receptor (GPCR) GPR55 drives skin tumor development and aggressiveness in mice. Upregulation in human tumors suggests GPR55 as a potential biomarker and therapeutic target for squamous cell carcinomas.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • G protein-coupled receptors (GPCRs) are vital in physiology and disease, including cancer.
  • The orphan receptor GPR55's role in cancer pathogenesis remains largely unknown.
  • Previous studies suggest GPR55 influences cancer cell behavior in vitro and in xenografts.

Purpose of the Study:

  • To investigate the in vivo role of GPR55 in skin tumor development and aggressiveness.
  • To assess GPR55's functional impact in clinically-relevant cancer models.
  • To explore GPR55 as a potential biomarker and therapeutic target in squamous cell carcinomas.

Main Methods:

  • Utilized GPR55-deficient and wild-type mice in a DMBA/TPA-induced skin carcinogenesis model.
  • Assessed tumor development, papilloma and carcinoma formation rates.
  • Evaluated cancer cell proliferation, anchorage-independent growth, invasiveness, and in vivo tumorigenicity.
  • Compared GPR55 expression levels in human skin tumors and squamous cell carcinomas versus healthy tissues.

Main Results:

  • GPR55-deficient mice exhibited resistance to DMBA/TPA-induced skin tumor formation.
  • GPR55 promoted tumor development by enhancing cancer cell proliferation.
  • GPR55 increased cancer cell invasiveness, anchorage-independent growth, and tumorigenicity.
  • GPR55 was found to be upregulated in human skin tumors and squamous cell carcinomas.

Conclusions:

  • GPR55 plays a critical role in driving mouse skin tumor development and aggressiveness.
  • GPR55 enhances key hallmarks of cancer, including proliferation and invasiveness.
  • Upregulated GPR55 in human squamous cell carcinomas indicates its potential as a biomarker and therapeutic target.

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