title: Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression.
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.
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Bearsden, Glasgow, G61 1BD, United Kingdom. g.mclean@beatson.gla.ac.uk
authors.forename: Gordon W
authors.initials: GW
authors.lastname: McLean
authors.forename: Noboru H
authors.initials: NH
authors.lastname: Komiyama
authors.forename: Bryan
authors.initials: B
authors.lastname: Serrels
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Asano
authors.forename: Louise
authors.initials: L
authors.lastname: Reynolds
authors.forename: Francesco
authors.initials: F
authors.lastname: Conti
authors.forename: Kairbaan
authors.initials: K
authors.lastname: Hodivala-Dilke
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Seth G N
authors.initials: SG
authors.lastname: Grant
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Frame
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D017931:DNA Primers; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D017353:Gene Deletion; D005838:Genotype; D006915:Hydroxytestosterones / Q000378:metabolism; D007150:Immunohistochemistry; D019426:Integrases / Q000378:metabolism; D053547:Keratin-14; D015603:Keratinocytes / Q000502:physiology; D007633:Keratins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000517:prevention & control; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011960:Receptors, Estrogen / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D006915:Hydroxytestosterones; D053547:Keratin-14; C507446:Krt14 protein, mouse; D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene; C032278:4,17 beta-dihydroxy-4-androstene-3-one; D015127:9,10-Dimethyl-1,2-benzanthracene; D007633:Keratins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; C045073:Cre recombinase; D019426:Integrases