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

Gordon W McLean; Noboru H Komiyama; Bryan Serrels; Hidefumi Asano; Louise Reynolds; Francesco Conti; Kairbaan Hodivala-Dilke; Daniel Metzger; Pierre Chambon; Seth G N Grant; Margaret C Frame

doi:10.1101/gad.316304

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

Gordon W McLean, Noboru H Komiyama, Bryan Serrels, Hidefumi Asano, Louise Reynolds, Francesco Conti, Kairbaan Hodivala-Dilke, Daniel Metzger, Pierre Chambon, Seth G N Grant, Margaret C Frame

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	2998-3003
Number of pages	6
Journal	Genes & Development
Volume	18
Issue number	24
DOIs	https://doi.org/10.1101/gad.316304
Publication status	Published - 15 Dec 2004

Keywords / Materials (for Non-textual outputs)

9,10-Dimethyl-1,2-benzanthracene
Animals
Apoptosis
Blotting, Western
DNA Primers
Flow Cytometry
Fluorescent Antibody Technique
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Gene Deletion
Genotype
Hydroxytestosterones
Immunohistochemistry
Integrases
Keratin-14
Keratinocytes
Keratins
Mice
Mice, Transgenic
Neoplasm Metastasis
Protein-Tyrosine Kinases
Receptors, Estrogen
Skin Neoplasms
Tamoxifen

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10.1101/gad.316304

Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression
Copyright © 2004, Cold Spring Harbor Laboratory Press
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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.",

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author = "McLean, {Gordon W} and Komiyama, {Noboru H} and Bryan Serrels and Hidefumi Asano and Louise Reynolds and Francesco Conti and Kairbaan Hodivala-Dilke and Daniel Metzger and Pierre Chambon and Grant, {Seth G N} and Frame, {Margaret C}",

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AU - McLean, Gordon W

AU - Komiyama, Noboru H

AU - Serrels, Bryan

AU - Asano, Hidefumi

AU - Reynolds, Louise

AU - Conti, Francesco

AU - Hodivala-Dilke, Kairbaan

AU - Metzger, Daniel

AU - Chambon, Pierre

AU - Grant, Seth G N

AU - Frame, Margaret C

PY - 2004/12/15

Y1 - 2004/12/15

N2 - 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.

AB - 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.

KW - 9,10-Dimethyl-1,2-benzanthracene

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KW - Apoptosis

KW - Blotting, Western

KW - DNA Primers

KW - Flow Cytometry

KW - Fluorescent Antibody Technique

KW - Focal Adhesion Kinase 1

KW - Focal Adhesion Protein-Tyrosine Kinases

KW - Gene Deletion

KW - Genotype

KW - Hydroxytestosterones

KW - Immunohistochemistry

KW - Integrases

KW - Keratin-14

KW - Keratinocytes

KW - Keratins

KW - Mice

KW - Mice, Transgenic

KW - Neoplasm Metastasis

KW - Protein-Tyrosine Kinases

KW - Receptors, Estrogen

KW - Skin Neoplasms

KW - Tamoxifen

U2 - 10.1101/gad.316304

DO - 10.1101/gad.316304

M3 - Article

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SN - 0890-9369

VL - 18

SP - 2998

EP - 3003

JO - Genes & Development

JF - Genes & Development

IS - 24

ER -

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

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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