Year: 2019
Type: article
Abstract: Mutations associated with tumor development in certain tissues can be nontumorigenic in others, yet the mechanisms underlying these different outcomes remains poorly understood. To address this, we targeted an activating Hras mutation to hair follicle stem cells and discovered that Hras mutant cells outcompete wild-type neighbors yet are integrated into clinically normal skin hair follicles. In contrast, targeting the Hras mutation to the upper noncycling region of the skin epithelium leads to benign outgrowths. Follicular Hras mutant cells autonomously and nonautonomously enhance regeneration, which directs mutant cells into continuous tissue cycling to promote integration rather than aberrancy. This follicular tolerance is maintained under additional challenges that promote tumorigenesis in the epidermis, including aging, injury, and a secondary mutation. Thus, the hair follicle possesses a unique, enhanced capacity to integrate and contain Hras mutant cells within both homeostatic and perturbed tissue, demonstrating that in the skin, multiple, distinct mechanisms exist to suppress oncogenic growth.
Source: The Journal of Cell Biology
Institutions: Yale University, Fred Hutch Cancer Center, Yale Cancer Center
Language: English
Topic: Hair Growth and Disorders
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Howard Hughes Medical Institute, Glenn Foundation for Medical Research, New York Stem Cell Foundation, Yale University, Vanderbilt University, Yale Cancer Center, Edward Mallinckrodt, Jr. Foundation, Leidos, Fondation pour la Recherche Médicale, National Institutes of Health, Yale School of Medicine, Yale College, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: Live Imaging of Skin Regeneration, G1719332228, G2683130771, Understanding Skin Tissue Repair in Live Mammals, Normal stem cells and their transition to disease in the skin, G4915471883, Predoctoral Training Program in Genetics, A novel lineage pathway controls metabolic adaptation by metastatic lung cancers, G9000176093
OpenAlex ID: W2972208107