摘要
Kindlin-1 is an integrin tail binding protein that controls integrin activation. Mutations in the FERMT-1 gene, which encodes for Kindlin-1, lead to Kindler syndrome in man, which is characterized by skin blistering, premature skin aging and skin cancer of unknown etiology. Here we show that loss of Kindlin-1 in mouse keratinocytes recapitulates Kindler syndrome and also produces enlarged and hyperactive stem cell compartments, which lead to hyperthickened epidermis, ectopic hair follicle development and increased skin tumor susceptibility. Mechanistically, Kindlin-1 controls keratinocyte adhesion through β 1 -class integrins and proliferation and differentiation of cutaneous epithelial stem cells by promoting αv β 6 integrin-mediated transforming growth factor-β (TGF-β) activation and inhibiting Wnt-β-catenin signaling through integrin-independent regulation of Wnt ligand expression. Our findings assign Kindlin-1 the previously unknown and essential task of controlling cutaneous epithelial stem cell homeostasis by balancing TGF-β-mediated growth-inhibitory signals and Wnt-β-catenin- mediated growth-promoting signals.
原文 | English |
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頁(從 - 到) | 350-359 |
頁數 | 10 |
期刊 | Nature Medicine |
卷 | 20 |
發行號 | 4 |
DOIs | |
出版狀態 | Published - 2014 4月 |
All Science Journal Classification (ASJC) codes
- 一般生物化學,遺傳學和分子生物學