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Updated: May 20, 2026

In Vivo CRISPR/Cas9 Screening to Simultaneously Evaluate Gene Function in Mouse Skin and Oral Cavity
Published on: November 2, 2020
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.
Abstract:
G protein-coupled receptors (GPCRs) control crucial physiological processes and their dysfunction contributes to various human diseases, including cancer. The orphan GPCR GPR55 was identified and cloned more than a decade ago, but very little is known about its physio-pathological relevance. It has been recently shown that GPR55 controls the behavior of human cancer cell lines in culture and xenografts. However, the assessment of the actual role of this receptor in malignant transformation in vivo is hampered by the lack of studies on its functional impact in clinically-relevant models of cancer. Here we demonstrate that GPR55 drives mouse skin tumor development. Thus, GPR55-deficient mice were more resistant to DMBA/TPA-induced papilloma and carcinoma formation than their wild-type littermates. GPR55 exerted this pro-tumor effect primarily by conferring a proliferative advantage on cancer cells. In addition, GPR55 enhanced skin cancer cell anchorage-independent growth, invasiveness and tumorigenicity in vivo, suggesting that it promotes not only tumor development but also tumor aggressiveness. Finally, we observed that GPR55 is upregulated in human skin tumors and other human squamous cell carcinomas compared with the corresponding healthy tissues. Altogether, these findings reveal the pivotal importance of GPR55 in skin tumor development, and suggest that this receptor may be used as a new biomarker and therapeutic target in squamous cell carcinomas.
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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