Involvement of focal adhesion kinase in the progression and prognosis of gastrointestinal stromal tumors.
Gastrointestinal stromal tumors often express gene mutations to c-KIT and platelet-derived growth factor receptor-alpha, both of which result in constitutive activations of their signaling pathways that are quite essential for the proliferation and survival of tumor cells in most clinical gastrointestinal stromal tumors. Targeting these molecules provides a dramatic improvement to therapeutic strategy. To identify a new therapeutic target for gastrointestinal stromal tumor treatment, we focused on focal adhesion kinase, which is reported to be an up-regulated gene in clinical gastrointestinal stromal tumors, because so far no one has examined its expression status at the protein level. In this study, Western blot analysis revealed that all 10 of the examined gastrointestinal stromal tumor tissues strongly expressed focal adhesion kinase protein and that phosphorylated focal adhesion kinase was detected in 9 of them. Next, we assessed the expression status of focal adhesion kinase and phosphorylated focal adhesion kinase in 51 cases of gastrointestinal stromal tumor by immunohistochemistry. Positive stainings for focal adhesion kinase and phosphorylated focal adhesion kinase were confirmed in 44 (86.3%) and in 40 cases (78.4%) of the 51 gastrointestinal stromal tumors, respectively. We further found that the focal adhesion kinase-positive staining rate became higher along with the increased status of malignant behavior. Moreover, when the 51 gastrointestinal stromal tumors were divided into 2 groups based upon their focal adhesion kinase expression status, the 5-year overall survival of patients in the focal adhesion kinase-positive group (66.5%) was significantly poorer than that in the focal adhesion kinase-negative group (100%). These results indicate that the up-regulation of focal adhesion kinase protein may also contribute to the tumor progression of gastrointestinal stromal tumors and that focal adhesion kinase is a potential target for gastrointestinal stromal tumor treatment.
Kamo
Nobuyuki
N
Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
Naomoto
Yoshio
Y
Shirakawa
Yasuhiro
Y
Yamatsuji
Tomoki
T
Hirota
Seiichi
S
Fujiwara
Yasuhiro
Y
Noma
Kazuhiro
K
Sakurama
Kazufumi
K
Takaoka
Munenori
M
Nagatsuka
Hitoshi
H
Gunduz
Mehmet
M
Matsuoka
Junji
J
Tanaka
Noriaki
N
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D018450:Disease Progression; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D018952:Antigens, CD34; D019089:Stem Cell Factor; D051416:Focal Adhesion Protein-Tyrosine Kinases