Focal adhesion kinase (FAK) has been implicated in
tumorigenesis in various
cancers; however, it remains unclear how FAK participates in
tumor malignancy in vivo. This study seeks to understand the role of FAK activation in
gastric cancer progression. Using immunohistochemical staining and Western blotting, we found that pY397 FAK, an autophosphorylation site on FAK activation, was abundant in the cancerous tissues of 21 of 59 patients with gastric
carcinomas. We attempted to correlate clinicopathological parameters, including histological types, TNM staging, and
cancer recurrence, with the expression of FAK and pY397 FAK in cancerous tissues. Intriguingly, patients with higher levels of pY397 FAK displayed higher incidences of
gastric cancer recurrence after surgery and poor 5-year recurrence-free survival. Furthermore, multivariate analyses showed that pY397 FAK was an independent predictor of
gastric cancer recurrence. As a result, expression of pY397 FAK is a significant prognostic factor for the recurrence of
gastric cancer. Additionally, in vitro studies showed that overexpression of Y397F, a dominant-negative mutant of FAK, in AGS human gastric
carcinoma cells impaired cell migration, invasion, and proliferation compared with cells overexpressing wild-type FAK. Thus, activation of FAK through autophosphorylation at Tyr397 leads to the progression of gastric
carcinomas by promoting cell migration, invasion, and proliferation. Collectively, our results have provided valuable insights for the development of novel diagnoses and therapeutic targets for
gastric cancer treatments.