Phosphorylation of focal adhesion kinase at Tyr397 in gastric carcinomas and its clinical significance.
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.
Lai
I-Rue
IR
Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
Chu
Pei-Yu
PY
Lin
Hsiao-Sheng
HS
Liou
Jun-Yang
JY
Jan
Yee-Jee
YJ
Lee
Jen-Chieh
JC
Shen
Tang-Long
TL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007414:Intestinal Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000201:enzymology* / Q000601:surgery; D010766:Phosphorylation; D013270:Stomach / Q000201:enzymology / Q000473:pathology; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
D051416:Focal Adhesion Protein-Tyrosine Kinases