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

被引:185
作者
McLean, GW
Komiyama, NH
Serrels, B
Asano, H
Reynolds, L
Conti, F
Hodivala-Dilke, K
Metzger, D
Chambon, P
Grant, SGN
Frame, MC
机构
[1] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland
[2] Univ Glasgow, Inst Biol & Life Sci, Glasgow G12 8QQ, Lanark, Scotland
[3] Univ Edinburgh, Div Neurosci, Edinburgh EH8 9JZ, Midlothian, Scotland
[4] London Queen Marys Sch Med & Dent, John Vane Sci Ctr, London EC1M 6BQ, England
[5] Coll France, CNRS, Inst Genet & Biol Mol & Cellulaire, INSERM,ULP, F-67404 Illkirch Graffenstaden, France
关键词
focal adhesion kinase; conditional; cancer; keratinocyte; apoptosis;
D O I
10.1101/gad.316304
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:2998 / 3003
页数:6
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