Inhibition of focal adhesion kinase induces apoptosis in bladder cancer cells via Src and the phosphatidylinositol 3-kinase/Akt pathway
Open Access
- 11 September 2015
- journal article
- Published by Spandidos Publications in Experimental and Therapeutic Medicine
- Vol. 10 (5), 1725-1731
- https://doi.org/10.3892/etm.2015.2745
Abstract
Focal adhesion kinase (FAK) is a 125-kDa, cytosolic, non-receptor, protein tyrosine kinase localized at focal adhesions that can be activated by multiple inputs and in different manners. FAK is implicated in signaling pathways regulating cell movement, invasion, survival, gene expression and cancer stem cell self-renewal. The aim of the present study was to investigate whether FAK plays a role in the apoptosis of bladder cancer cells. The study employed in situ deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and Annexin V labeling flow cytometry. It was found that both the knockdown of FAK and the suppression of FAK phosphorylation were able to induce apoptosis in bladder cancer cells. Caspase-3 was activated during the apoptosis induced by the suppression of FAK phosphorylation. Src was involved in FAK-regulated apoptosis in bladder cancer cells, while the suppression of Src phosphorylation was able to inhibit FAK tyrosine phosphorylation and induce apoptosis. Furthermore, phosphatidylinositol 3-kinase (PI3K)/Akt signaling was inhibited via the suppression of FAK tyrosine phosphorylation. Conversely, the expression of neither the general nor the tyrosine-phosphorylated FAK was regulated by inhibiting PI3K/Akt, which suggested that PI3K/Akt acted downstream of FAK to regulate apoptosis in bladder cancer cells. These findings indicate the presence of a mechanism of apoptosis involving FAK-mediated oncogenic signaling. FAK may function as an important regulator of extracellular signaling-mediated apoptosis in bladder cancer and be used as a novel therapeutic target in the treatment of the condition.Keywords
This publication has 48 references indexed in Scilit:
- Comprehensive molecular portraits of human breast tumoursNature, 2012
- Integrated genomic analyses of ovarian carcinomaNature, 2011
- Tumor-initiating stem cells of squamous cell carcinomas and their control by TGF-β and integrin/focal adhesion kinase (FAK) signalingProceedings of the National Academy of Sciences of the United States of America, 2011
- Transforming growth factor-β-induced epithelial–mesenchymal transition facilitates epidermal growth factor-dependent breast cancer progressionOncogene, 2010
- Cellular functions of FAK kinases: insight into molecular mechanisms and novel functionsJournal of Cell Science, 2010
- Focal adhesion kinase: A prominent determinant in breast cancer initiation, progression and metastasisCancer Letters, 2010
- FAK alters invadopodia and focal adhesion composition and dynamics to regulate breast cancer invasionThe Journal of cell biology, 2009
- Transforming Growth Factor β Induces Clustering of HER2 and Integrins by Activating Src-Focal Adhesion Kinase and Receptor Association to the CytoskeletonCancer Research, 2009
- PTK2 and EIF3S3 genes may be amplification targets at 8q23-q24 and are associated with large hepatocellular carcinomasJournal of Hepatology, 2003
- A Suppressive Role of p125FAK Protein Tyrosine Kinase in Hydrogen Peroxide-Induced Apoptosis of T98G CellsBiochemical and Biophysical Research Communications, 1997