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Updated: Jul 20, 2026
Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
Decreased focal adhesion kinase suppresses papilloma formation during experimental mouse skin carcinogenesis
G W McLean1, K Brown, M I Arbuckle
1Beatson Institute for Cancer Research, Garscube Estate, Bearsden, Glasgow G61 1BD, United Kingdom.
Abstract:
Although focal adhesion kinase (FAK) is elevated in epithelial cancers, it is not known whether FAK expression influences tumor development in vivo. We found that fak +/- heterozygous mice display reduced 7,12-dimethylbenz[a]anthracene-induced papilloma formation that correlates with reduced FAK protein expression in the skin. However, the frequency of malignant conversion of papillomas into carcinomas is indistinguishable in fak +/- mice and their wild-type fak +/+ littermates, most likely because papilloma FAK protein expression is elevated to wild-type levels. We also found that keratinocyte FAK protein expression is important for cellular responses downstream of ras in vitro (monitored by extracellular signal-regulated kinase activation after integrin engagement). Because 7,12-dimethylbenz[a]anthracene induces an activating mutation of H-ras, this provides one possible explanation for suppression of papilloma formation when FAK protein is limiting.
Insights
Reduced focal adhesion kinase (FAK) expression in mice lowered tumor formation but did not affect malignant conversion. This suggests FAK is crucial for early tumor development, particularly in ras-driven cancers.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Focal adhesion kinase (FAK) is often elevated in epithelial cancers.
- The in vivo role of FAK in tumor development remains largely unexplored.
Purpose of the Study:
- To investigate the in vivo role of focal adhesion kinase (FAK) in tumor development.
- To determine if FAK expression levels influence the formation and malignant conversion of chemically induced skin tumors.
Main Methods:
- Utilized fak +/- heterozygous mice and wild-type fak +/+ littermates.
- Administered 7,12-dimethylbenz[a]anthracene to induce papilloma formation.
- Assessed FAK protein expression in skin and papillomas.
- Evaluated keratinocyte cellular responses downstream of ras activation in vitro.
Main Results:
- Fak +/- mice exhibited reduced 7,12-dimethylbenz[a]anthracene-induced papilloma formation, correlating with lower FAK protein levels in the skin.
- The rate of malignant conversion from papillomas to carcinomas was similar between fak +/- and fak +/+ mice.
- Elevated FAK protein levels in papillomas of fak +/- mice reached wild-type levels, potentially explaining the lack of difference in malignant conversion.
- Keratinocyte FAK protein expression was essential for downstream cellular responses to ras activation, such as extracellular signal-regulated kinase activation.
Conclusions:
- FAK protein expression is critical for the initiation of tumor development in vivo, especially in the context of ras mutations.
- While FAK limits initial tumor formation, its role in the malignant progression of established tumors may be compensated by other pathways.
![Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F60445.jpg&w=3840&q=50)
