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Keratinocytes enriched for stem cells are protected from anoikis via an integrin signaling pathway in a Bcl‐2 dependent manner
Author(s) -
Tiberio Rossana,
Marconi Alessandra,
Fila Chiara,
Fumelli Cristiana,
Pignatti Marco,
Krajewski Stan,
Giannetti Alberto,
Reed John C,
Pincelli Carlo
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03040-5
Subject(s) - anoikis , integrin , microbiology and biotechnology , stem cell , hacat , apoptosis , keratinocyte , biology , cell culture , cell , chemistry , programmed cell death , biochemistry , genetics
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.