https://scholars.lib.ntu.edu.tw/handle/123456789/473717
標題: | Phosphorylation of focal adhesion kinase at Tyr397 in gastric carcinomas and its clinical significance | 作者: | I-RUE LAI TANG-LONG SHEN Lin H.-S. Liou J.-Y. Jan Y.-J. JEN-CHIEH LEE |
公開日期: | 2010 | 出版社: | Elsevier Inc. | 卷: | 177 | 期: | 4 | 起(迄)頁: | 1629-1637 | 來源出版物: | American Journal of Pathology | 摘要: | 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. Copyright ? American Society for Investigative Pathology. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-77957350031&doi=10.2353%2fajpath.2010.100172&partnerID=40&md5=3881fc448d7d9319a23a0e9ce7180b87 https://scholars.lib.ntu.edu.tw/handle/123456789/473717 |
ISSN: | 0002-9440 | DOI: | 10.2353/ajpath.2010.100172 | SDG/關鍵字: | focal adhesion kinase; adult; aged; article; cancer invasion; cancer recurrence; cancer survival; cell migration; cell proliferation; female; histopathology; human; human tissue; immunohistochemistry; lymph node metastasis; major clinical study; male; priority journal; prognosis; protein expression; protein phosphorylation; stomach carcinogenesis; stomach carcinoma; tumor volume; Western blotting |
顯示於: | 病理學科所 |
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