Keratinocytes enriched for stem cells are protected from anoikis via an integrin signaling pathway in a Bcl-2 dependent manner

被引:79
作者
Tiberio, R
Marconi, A
Fila, C
Fumelli, C
Pignatti, M
Krajewski, S
Giannetti, A
Reed, JC
Pincelli, C
机构
[1] Univ Modena & Reggio Emilia, Dept Internal Med, Dermatol Sect, I-41100 Modena, Italy
[2] Burnham Inst, La Jolla, CA 92037 USA
来源
FEBS LETTERS | 2002年 / 524卷 / 1-3期
关键词
adhesion; extracellular matrix; anoikis; epidermis; p63; alpha; 6; beta; 4;
D O I
10.1016/S0014-5793(02)03040-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Because inhibition of integrin signaling induces apoptosis, we investigated whether keratinocytes expressing beta1 and alpha6beta4 integrins (enriched for stem cells) are protected from cell death. Keratinocytes rapidly adhering to type IV collagen expressed highest levels of beta1 and alpha6beta4 and of the anti-apoptotic stem cell marker p63. Apoptotic cells were significantly higher in slowly adhering than in rapidly adhering keratinocytes. Anti-beta1 integrin caused a significant increase in apoptotic cells, while it decreased Bcl-2 levels in stem keratinocytes. Bax and Bad proteins were higher in slowly adhering than in rapidly adhering cells. By contrast, Bcl-2, Bcl-x and Mcl-1 proteins were highest in rapidly adhering keratinocytes and nearly absent in slowly adhering cells. After addition of anti-beta1 integrin, the apoptotic rate was significantly higher in HaCaT cells not expressing Bcl-2 than in controls. These results indicate that keratinocytes enriched for stem cells are protected from apoptosis via beta1 integrin, in a Bcl-2 dependent manner. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
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页码:139 / 144
页数:6
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