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Published on: December 19, 2019
Exploiting Mouse Models to Study Ras-Induced Cutaneous Squamous Cell Carcinoma
William E Lowry1, Aimee Flores2, Andrew C White3
1Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, USA; Eli and Edythe Broad Center for Regenerative Medicine, University of California Los Angeles, Los Angeles, California, USA; Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, USA.
Abstract:
Recently developed methods have allowed for the delivery of cancer-causing genetic mutations to particular cell types in the epidermis in an inducible fashion. These methods have allowed for sophisticated explorations on the cellular and molecular origins of squamous cell carcinoma due to oncogenic mutations in Ras. These experiments have provided insights into whether cancer is initiated by stem or more specified cells under various conditions, and have highlighted the ability of particular genetic hits to serve as tumor initiators or promoters. Here we provide a summary of data from our lab and others that demonstrate the ability of hair follicle stem cells to serve as cancer cells of origin, and the ability of various molecular players to drive heterogeneity of tumor cell types. A synthesis of these studies potentially could provide unique insights into the process by which Ras can initiate squamous cell carcinoma in human patients and could eventually inform treatment strategies.
Insights
New methods enable inducible delivery of cancer mutations to skin cells. Hair follicle stem cells can initiate squamous cell carcinoma, with molecular factors driving tumor diversity, offering insights into Ras-driven cancer.
Area of Science:
- Dermatology
- Oncology
- Molecular Biology
Background:
- Recent advancements allow inducible delivery of oncogenic mutations to specific epidermal cell types.
- Understanding the cellular origins of squamous cell carcinoma (SCC) is crucial for developing effective treatments.
- Oncogenic mutations in Ras are implicated in the development of SCC.
Purpose of the Study:
- To summarize findings on the role of hair follicle stem cells (HFSCs) as cancer cells of origin in SCC.
- To explore how molecular players contribute to tumor cell type heterogeneity in Ras-driven SCC.
- To synthesize data providing insights into Ras-initiated SCC in human patients.
Main Methods:
- Utilizing inducible genetic methods to deliver oncogenic mutations to epidermal cells.
- Analyzing data from laboratory experiments and published studies.
- Investigating the initiation and promotion roles of specific genetic alterations.
Main Results:
- Hair follicle stem cells (HFSCs) can act as the cells of origin for SCC.
- Various molecular factors drive the heterogeneity observed in tumor cell types.
- Specific genetic mutations can function as either tumor initiators or promoters.
Conclusions:
- HFSCs are capable of initiating squamous cell carcinoma.
- Molecular mechanisms contribute significantly to the diversity of SCC tumor cells.
- This research offers insights into Ras-driven SCC pathogenesis and potential therapeutic strategies.
