Keratinocytes enriched for stem cells are protected from anoikis via an integrin signaling pathway in a Bcl-2 dependent manner.
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.
Tiberio
Rossana
R
Department of Internal Medicine, Section of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy.
Marconi
Alessandra
A
Fila
Chiara
C
Fumelli
Cristiana
C
Pignatti
Marco
M
Krajewski
Stan
S
Giannetti
Alberto
A
Reed
John C
JC
Pincelli
Carlo
C
D023102:Anoikis / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*
D016023:Integrins; D019253:Proto-Oncogene Proteins c-bcl-2