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Hair follicle regeneration suppresses Ras-driven oncogenic growth
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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781447/ https://www.ncbi.nlm.nih.gov/pubmed/31488583 http://dx.doi.org/10.1083/jcb.201907178 |
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author | Pineda, Cristiana M. Gonzalez, David G. Matte-Martone, Catherine Boucher, Jonathan Lathrop, Elizabeth Gallini, Sara Fons, Nathan R. Xin, Tianchi Tai, Karen Marsh, Edward Nguyen, Don X. Suozzi, Kathleen C. Beronja, Slobodan Greco, Valentina |
author_facet | Pineda, Cristiana M. Gonzalez, David G. Matte-Martone, Catherine Boucher, Jonathan Lathrop, Elizabeth Gallini, Sara Fons, Nathan R. Xin, Tianchi Tai, Karen Marsh, Edward Nguyen, Don X. Suozzi, Kathleen C. Beronja, Slobodan Greco, Valentina |
author_sort | Pineda, Cristiana M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6781447 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-67814472020-04-07 Hair follicle regeneration suppresses Ras-driven oncogenic growth Pineda, Cristiana M. Gonzalez, David G. Matte-Martone, Catherine Boucher, Jonathan Lathrop, Elizabeth Gallini, Sara Fons, Nathan R. Xin, Tianchi Tai, Karen Marsh, Edward Nguyen, Don X. Suozzi, Kathleen C. Beronja, Slobodan Greco, Valentina J Cell Biol Research Articles 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. Rockefeller University Press 2019-10-07 2019-09-05 /pmc/articles/PMC6781447/ /pubmed/31488583 http://dx.doi.org/10.1083/jcb.201907178 Text en © 2019 Pineda et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Pineda, Cristiana M. Gonzalez, David G. Matte-Martone, Catherine Boucher, Jonathan Lathrop, Elizabeth Gallini, Sara Fons, Nathan R. Xin, Tianchi Tai, Karen Marsh, Edward Nguyen, Don X. Suozzi, Kathleen C. Beronja, Slobodan Greco, Valentina Hair follicle regeneration suppresses Ras-driven oncogenic growth |
title | Hair follicle regeneration suppresses Ras-driven oncogenic growth |
title_full | Hair follicle regeneration suppresses Ras-driven oncogenic growth |
title_fullStr | Hair follicle regeneration suppresses Ras-driven oncogenic growth |
title_full_unstemmed | Hair follicle regeneration suppresses Ras-driven oncogenic growth |
title_short | Hair follicle regeneration suppresses Ras-driven oncogenic growth |
title_sort | hair follicle regeneration suppresses ras-driven oncogenic growth |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781447/ https://www.ncbi.nlm.nih.gov/pubmed/31488583 http://dx.doi.org/10.1083/jcb.201907178 |
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