IL-17R–EGFR axis links wound healing to tumorigenesis in Lrig1(+) stem cells

Lrig1 marks a distinct population of stem cells restricted to the upper pilosebaceous unit in normal epidermis. Here we report that IL-17A–mediated activation of EGFR plays a critical role in the expansion and migration of Lrig1(+) stem cells and their progenies in response to wounding, thereby prom...

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Detalles Bibliográficos
Autores principales: Chen, Xing, Cai, Gang, Liu, Caini, Zhao, Junjie, Gu, Chunfang, Wu, Ling, Hamilton, Thomas A., Zhang, Cun-jin, Ko, Jennifer, Zhu, Liang, Qin, Jun, Vidimos, Allison, Koyfman, Shlomo, Gastman, Brian R., Jensen, Kim B., Li, Xiaoxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314525/
https://www.ncbi.nlm.nih.gov/pubmed/30578323
http://dx.doi.org/10.1084/jem.20171849
Descripción
Sumario:Lrig1 marks a distinct population of stem cells restricted to the upper pilosebaceous unit in normal epidermis. Here we report that IL-17A–mediated activation of EGFR plays a critical role in the expansion and migration of Lrig1(+) stem cells and their progenies in response to wounding, thereby promoting wound healing and skin tumorigenesis. Lrig1-specific deletion of the IL-17R adaptor Act1 or EGFR in mice impairs wound healing and reduces tumor formation. Mechanistically, IL-17R recruits EGFR for IL-17A–mediated signaling in Lrig1(+) stem cells. While TRAF4, enriched in Lrig1(+) stem cells, tethers IL-17RA and EGFR, Act1 recruits c-Src for IL-17A–induced EGFR transactivation and downstream activation of ERK5, which promotes the expansion and migration of Lrig1(+) stem cells. This study demonstrates that IL-17A activates the IL-17R–EGFR axis in Lrig1(+) stem cells linking wound healing to tumorigenesis.

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