| First Author | Chen X | Year | 2019 |
| Journal | J Exp Med | Volume | 216 |
| Issue | 1 | Pages | 195-214 |
| PubMed ID | 30578323 | Mgi Jnum | J:273043 |
| Mgi Id | MGI:6284642 | Doi | 10.1084/jem.20171849 |
| Citation | Chen X, et al. (2019) IL-17R-EGFR axis links wound healing to tumorigenesis in Lrig1(+) stem cells. J Exp Med 216(1):195-214 |
| abstractText | 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. |
