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Published on: July 21, 2018
Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression
Gordon W McLean1, Noboru H Komiyama, Bryan Serrels
1The Beatson Institute for Cancer Research, Garscube Estate, Bearsden, Glasgow, G61 1BD, United Kingdom. g.mclean@beatson.gla.ac.uk
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.
Insights
This study shows that deleting the focal adhesion kinase (FAK) gene in mice suppresses skin tumor formation and progression. FAK deletion also increases skin cell death, impacting cancer development.
Area of Science:
- Oncology
- Dermatology
- Molecular Biology
Background:
- Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase.
- FAK plays a role in cell signaling pathways regulating cell proliferation, survival, and migration.
- The role of FAK in skin tumorigenesis is not fully understood.
Purpose of the Study:
- To investigate the role of FAK in skin tumor initiation and progression using a genetically engineered mouse model.
- To determine the effects of FAK deletion on keratinocyte behavior in vitro and in vivo.
Main Methods:
- Generated mice with a floxed FAK allele controlled by a keratin-14-driven Cre-estrogen receptor (CreER(T2)) system.
- Administered 4-hydroxy-tamoxifen to induce FAK deletion in the epidermis.
- Assessed chemically induced skin tumor formation and progression.
- Evaluated keratinocyte migration and cell death in vitro and in vivo.
- Examined wound re-epithelialization in vivo.
Main Results:
- FAK deletion in the epidermis suppressed chemically induced skin tumor formation.
- Loss of FAK inhibited malignant progression of existing benign tumors.
- FAK deletion reduced keratinocyte migration in vitro but did not affect wound re-epithelialization in vivo.
- Increased keratinocyte cell death (apoptosis) was observed both in vitro and in vivo following FAK deletion.
Conclusions:
- This study provides the first experimental evidence implicating FAK in skin tumorigenesis.
- FAK plays a critical role in promoting skin tumor development and progression.
- FAK inhibition may represent a potential therapeutic strategy for skin cancer by promoting apoptosis.
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