Simultaneous inhibition of focal adhesion kinase and SRC enhances detachment and apoptosis in colon cancer cell lines

Vita M Golubovskaya; Steven Gross; Aparna S Kaur; Richard I Wilson; Li-Hui Xu; Xi Hui Yang; William G Cance

Simultaneous inhibition of focal adhesion kinase and SRC enhances detachment and apoptosis in colon cancer cell lines

Mol Cancer Res. 2003 Aug;1(10):755-64.

Authors

Vita M Golubovskaya¹, Steven Gross, Aparna S Kaur, Richard I Wilson, Li-Hui Xu, Xi Hui Yang, William G Cance

Affiliation

¹ Department of Surgery, University of Florida, Gainesville, FL 32610-0286, USA.

PMID: 12939401

Abstract

Focal adhesion kinase (FAK) and Src have been shown to be overexpressed in colon cancer. We have studied the role of these two kinases in resistance to apoptosis. Adenovirus-containing FAK-CD (Ad-FAK-CD), a dominant-negative, COOH-terminal portion of FAK, was used to inhibit FAK and cause apoptosis. Colon cancer cell lines were more resistant to Ad-FAK-CD-induced detachment and apoptosis than the breast cancer cell line, BT474. Colon cancer cell lines overexpressed highly active Src and FAK. Ad-FAK-CD-induced apoptosis was significantly increased by PP2, an inhibitor of Src family kinases. Activation of caspase-3, down-regulation of FAK, and Src and AKT activities were demonstrated in Ad-FAK-CD + PP2-treated colon cancer cells undergoing apoptosis. The results suggest that FAK and Src are both important survival factors, playing a role in protecting colon cancer cell lines from Ad-FAK-CD-induced apoptosis. Dual inhibition of these kinases may be important for therapies designed to enhance the apoptosis in colon cancers.

MeSH terms

Adenoviridae / genetics
Adenoviridae / metabolism
Apoptosis / drug effects
Apoptosis / physiology*
Blotting, Western
Caspase 3
Caspases / metabolism
Cell Adhesion* / drug effects
Cell Line, Tumor
Down-Regulation
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
HT29 Cells
Humans
Immunoblotting
Microscopy, Fluorescence
Protein Serine-Threonine Kinases*
Protein-Tyrosine Kinases / antagonists & inhibitors
Protein-Tyrosine Kinases / genetics
Protein-Tyrosine Kinases / metabolism*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
Pyrimidines / pharmacology
Signal Transduction
Staurosporine / pharmacology
src-Family Kinases / antagonists & inhibitors
src-Family Kinases / metabolism*

Substances

AG 1879
Proto-Oncogene Proteins
Pyrimidines
Protein-Tyrosine Kinases
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
PTK2 protein, human
src-Family Kinases
AKT1 protein, human
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins c-akt
CASP3 protein, human
Caspase 3
Caspases
Staurosporine