A Polymorphic Variant of AFAP-110 Enhances cSrc Activity
David A Clump1, Jing Jie Yu, Youngjin Cho
1The Mary Babb Randolph Cancer Center and the Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV, USA.
Translational Oncology
|August 7, 2010
Summary
Enhanced levels of c-Src (a protein tyrosine kinase) and AFAP-110 correlate with ovarian cancer progression. A specific AFAP-110 genetic variant can activate c-Src, potentially driving cancer growth.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Elevated c-Src activity is linked to ovarian cancer progression.
- c-Src activity is regulated by conformational changes, not typically mutations.
- AFAP-110 is a protein that activates c-Src by disrupting its autoinhibition.
Purpose of the Study:
- To investigate the role of AFAP-110 in ovarian cancer.
- To analyze the expression of AFAP-110 and c-Src in ovarian cancer tissues.
- To determine the functional impact of an AFAP-110 genetic variant on c-Src activity.
Main Methods:
- Immunohistochemical analysis of ovarian cancer tissues.
- Sequencing of the AFAP-110 coding sequence.
- Cellular assays to assess c-Src activation and podosome formation.
Main Results:
- Concomitant increase in AFAP-110 and c-Src expression in ovarian cancer tissues.
- Identification of a single-nucleotide polymorphism in AFAP-110 (Ser403 to Cys403).
- The AFAP-110(403C) variant activates c-Src and promotes podosome formation independently of signals in cells with high c-Src levels.
Conclusions:
- Overexpressed AFAP-110, particularly the polymorphic variant (403C), can promote c-Src activation in ovarian cancer.
- Inherited genetic variations in AFAP-110 may influence ovarian cancer progression.
- This mechanism could serve as a predictive marker for targeted therapy response in ovarian cancer.
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