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

Gordon W. Mclean (1) , Noboru H. Komiyama (2, 3) , Bryan Serrels (1) , Hidefumi Asano (3) , Louise Reynolds (4) , Francesco Conti (4) , Kairbaan Hodivala-Dilke (4) , Daniel Metzger (5) , Pierre Chambon (5) , Seth G.N. Grant (2, 3) , Margaret C. Frame (1, 6)

1 The Beatson Institute for Cancer Research
2 The Wellcome Trust Sanger Institute [Cambridge]
3 Edin. - University of Edinburgh
4 Queen Mary's School of Medicine and Dentistry
5 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
6 University of Glasgow

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.

Domaines: Génétique

Gordon W. Mclean, Noboru H. Komiyama, Bryan Serrels, Hidefumi Asano, Louise Reynolds, et al.. Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression. Genes and Development, 2004, 18 (24), pp.2998-3003. ⟨10.1101/gad.316304⟩. ⟨hal-04138419⟩