Hair follicle regeneration suppresses Ras-driven oncogenic growth
- PMID: 31488583
- PMCID: PMC6781447
- DOI: 10.1083/jcb.201907178
Hair follicle regeneration suppresses Ras-driven oncogenic growth
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.
© 2019 Pineda et al.
Figures
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Comment in
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Adult hair follicles keep oncogenic growth in check.J Cell Biol. 2019 Oct 7;218(10):3163-3165. doi: 10.1083/jcb.201909042. Epub 2019 Sep 19. J Cell Biol. 2019. PMID: 31537713 Free PMC article.
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