Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression

Gordon W. McLean(Cancer Research UK Scotland Institute), Noboru H. Komiyama(Centre National de la Recherche Scientifique), Bryan Serrels(Centre National de la Recherche Scientifique), Hidefumi Asano(Centre National de la Recherche Scientifique), Louise E. Reynolds(Centre National de la Recherche Scientifique), Francesco J. Conti(Centre National de la Recherche Scientifique), Kairbaan Hodivala‐Dilke(Centre National de la Recherche Scientifique), Daniel METZGER(Centre National de la Recherche Scientifique), Pierre Chambon(Centre National de la Recherche Scientifique), Seth G. N. Grant(Centre National de la Recherche Scientifique), Margaret C. Frame(Centre National de la Recherche Scientifique)
Genes & Development
December 15, 2004
Cited by 218Open Access
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Abstract

We have generated mice with a floxed fak allele under the control of keratin-14-driven Cre fused to a modified estrogen receptor (CreER(T2)). 4-Hydroxy-tamoxifen treatment induced fak deletion in the epidermis, and suppressed chemically induced skin tumor formation. Loss of fak induced once benign tumors had formed inhibited malignant progression. Although fak deletion was associated with reduced migration of keratinocytes in vitro, we found no effect on wound re-epithelialization in vivo. However, increased keratinocyte cell death was observed after fak deletion in vitro and in vivo. Our work provides the first experimental proof implicating FAK in tumorigenesis, and this is associated with enhanced apoptosis.


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