Focal adhesion kinase regulates the phosphorylation protein tyrosine phosphatase-α at Tyr789 in breast cancer cells.

Protein tyrosine phosphatase (PTP)‑α regulates the phosphorylation of focal adhesion kinase (FAK), which is important in cellular signal transduction and integration of proteins. It has been demonstrated that a FAK‑Del33 mutation (deletion of exon 33; KF437463) in breast cancer tissues regulates cell migration through FAK/Src signaling activation. However, the detailed pathway for Src activation with FAK‑Del33 remains to be elucidated. The present study used a retroviral expression system to examine changes in PTPα phosphorylation affected by the FAK‑Del33 protein in breast cancer cells. Small interfering (si)RNA targeting PTPα interfered with the phosphorylation of Src. Wound‑healing and migration assays were performed to identify cell morphology and quantitative analysis was performed by examining band color depth in western blot analysis. Significant differences were observed in the phosphorylation level of PTPα at Tyr789 between the FAK‑Del33 and the wild‑type breast cancer cells, suggesting that FAK regulated the phosphorylation level of PTPα at Tyr789 in breast cancer mutant FAK‑Del33 cells. The gene expression profile with FAK siRNA did not alter the levels of phosphorylation in other mutants, including autophosphorylation disability (Y397F), ATP kinase dominant negative (K454R) and protein 4.1, ezrin, radixin, moesin domain attenuate (Δ375). FAK RNAi inhibited the activity of the FAK‑Del33 at the Src site and rescued the elevated cell migration and invasion. The present study demonstrated for the first time, to the best of our knowledge, an increase in the phosphorylation level of PTPα‑Tyr789 by its upstream activator, FAK‑Del33, leading to Src activation in certain breast cancer cells, which has significant implications for metastatic potential.