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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
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.
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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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