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

FEBS Letters

Giannetti, Alberto²  Reed, John C¹  Fumelli, Cristiana²  Tiberio, Rossana²  Pignatti, Marco²  Pincelli, Carlo²  Krajewski, Stan¹  Marconi, Alessandra²  Fila, Chiara² 

[1] The Burnham Institute, La Jolla, CA, USA;Department of Internal Medicine, Section of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy

关键词: Adhesion;    Extracellular matrix;    Anoikis;    Epidermis;    p63;    α6β4;    ECM;    extracellular matrix;    CFE;    colony forming efficiency;    TA;    transit amplifying;   

DOI  :  10.1016/S0014-5793(02)03040-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Because inhibition of integrin signaling induces apoptosis, we investigated whether keratinocytes expressing β1 and α6β4 integrins (enriched for stem cells) are protected from cell death. Keratinocytes rapidly adhering to type IV collagen expressed highest levels of β1 and α6β4 and of the anti-apoptotic stem cell marker p63. Apoptotic cells were significantly higher in slowly adhering than in rapidly adhering keratinocytes. Anti-β1 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-β1 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 β1 integrin, in a Bcl-2 dependent manner.

【 授权许可】

Unknown