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Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
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Lgr6 is a stem cell marker in mouse skin squamous cell carcinoma
Phillips Y Huang1,2, Eve Kandyba1, Arnaud Jabouille1
1Helen Diller Family Comprehensive Cancer Center University of California, San Francisco, San Francisco, California, USA.
Nature Genetics
|September 26, 2017
Summary
Lgr6 acts as an epithelial stem cell marker in squamous cell carcinoma (SCC). Loss of Lgr6 predisposes mice to SCC, highlighting its role in tumor suppression and Wnt signaling pathways.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- G-protein-coupled receptors LGR4, LGR5, and LGR6 are Wnt signaling mediators.
- Their precise roles in squamous cell carcinoma (SCC) remain largely undefined.
Purpose of the Study:
- To investigate the function of LGR4, LGR5, and LGR6 in SCC.
- To identify epithelial stem cell markers in SCC and understand their role in tumor development.
Main Methods:
- Lineage tracing using Lgr5-EGFP-CreERT2/Rosa26-Tomato and Lgr6-EGFP-CreERT2/Rosa26-Tomato reporter mice.
- Single-molecule in situ hybridization and cell sorting to identify Lgr6-expressing cells.
- Germline knockout of Lgr6 in mice to assess SCC predisposition.
Main Results:
- Lgr6, not Lgr5, functions as an epithelial stem cell marker in SCC in vivo.
- Lgr6 expression is elevated in advanced SCCs and enriched in stem-like cells.
- Lgr6 downregulation increases epidermal proliferation and expands stem cell lineage tracing.
- Lgr6 knockout mice exhibit SCC predisposition, with compensatory Lgr5 upregulation.
Conclusions:
- Lgr6 plays a critical role in SCC suppression, acting as an epithelial stem cell marker.
- Loss of Lgr6 function contributes to SCC development, potentially through compensatory Wnt pathway alterations.
- Findings offer insights into human SCC susceptibility linked to germline mutations in Wnt pathway genes like RSPO1 and LGR4.
