Phosphorylation of focal adhesion kinase at Tyr397 in gastric carcinomas and its clinical significance

Am J Pathol. 2010 Oct;177(4):1629-37. doi: 10.2353/ajpath.2010.100172. Epub 2010 Aug 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Cell Adhesion
  • Cell Movement*
  • Cell Proliferation
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Intestinal Neoplasms / enzymology*
  • Intestinal Neoplasms / pathology
  • Intestinal Neoplasms / surgery
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / enzymology*
  • Neoplasm Recurrence, Local / surgery
  • Phosphorylation
  • Stomach / enzymology
  • Stomach / pathology
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Survival Rate
  • Tissue Array Analysis
  • Tumor Cells, Cultured

Substances

  • Focal Adhesion Protein-Tyrosine Kinases