title: Exploiting Mouse Models to Study Ras-Induced Cutaneous Squamous Cell Carcinoma.
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.
authors.affiliation: Molecular 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. Electronic address: blowry@ucla.edu.
authors.forename: William E
authors.initials: WE
authors.lastname: Lowry
authors.affiliation: Molecular Cell and Developmental Biology, 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.
authors.forename: Aimee
authors.initials: A
authors.lastname: Flores
authors.affiliation: Cornell University Stem Cell Program, Cornell University, Ithaca, New York, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: White
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D004817:Epidermis / Q000473:pathology; D014644:Genetic Variation; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009857:Oncogenes; D010641:Phenotype; D011401:Promoter Regions, Genetic; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; C116884:LGR5 protein, human; C417544:LGR6 protein, human; D043562:Receptors, G-Protein-Coupled; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins