Prognostic value of integrin beta1-ILK-pAkt signaling pathway in non-small cell lung cancer.
Cell adhesion signaling via the integrin-extracellular matrix connection plays a critical role in the growth and survival of normal adhering cells. Integrin-linked kinase is a ubiquitously expressed serine-threonine protein kinase capable of interacting with the cytoplasmic domains of integrin beta1 and beta3 and plays a critical role of an interface between integrin and the cytoskeleton in integrin-dependent cell adhesion, spreading, and cell shape change. In this study, we evaluated integrin beta1, integrin-linked kinase, and phosphorylated-Akt (Ser 473; pAkt) expressions in 118 consecutive non-small cell lung cancer tissue samples surgically resected between 1997 and 2000. As a result, we identified the specific subset of strong membranous staining of integrin beta1, strong cytoplasmic staining of integrin-linked kinase, and strong cytoplasmic staining with a granular pattern of pAkt in the non-small cell lung cancer tissue samples. In addition, we provide evidence that integrin-linked kinase, integrin beta1, and the activated form of Akt are mutually associated with poor prognosis in non-small cell lung cancer and that the simultaneous overexpression of these proteins is an independent prognostic factor (hazard ratio, 2.771; P = .003) comparable with standard prognostic factors such as T factor and lymphatic invasion by multivariate analysis. Thus, further studies of the integrin beta1-integrin-linked kinase-pAkt signaling pathway may provide a novel prognostic marker and therapeutic target for non-small cell lung cancer.
Okamura
Mayumi
M
Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Yamaji
Satoshi
S
Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: yamaji@med.yokohama-cu.ac.jp.
Nagashima
Yoji
Y
Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Nishikawa
Masanori
M
Department of Respiratory Medicine, Fujisawa City Hospital, Fujisawa 251-8550, Japan.
Yoshimoto
Noboru
N
Department of Chest Surgery, Fujisawa City Hospital, Fujisawa 251-8550, Japan.
Kido
Yasuhiro
Y
Department of Chest Surgery, Fujisawa City Hospital, Fujisawa 251-8550, Japan.
Iemoto
Yoichi
Y
Department of Diagnostic Pathology, Fujisawa City Hospital, Fujisawa 251-8550, Japan.
Aoki
Ichiro
I
Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Ishigatsubo
Yoshiaki
Y
Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: ishigats@med.yokohama-cu.ac.jp.
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D016019:Survival Analysis; D000099200:Scaffold Protein ILK
D019012:Integrin beta1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000099200:Scaffold Protein ILK