Prognostic value of integrin β1-ILK-pAkt signaling pathway in non–small cell lung cancer

Summary 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 β 1 and β 3 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 β 1, 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 β 1, 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 β 1, 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 β 1–integrin-linked kinase-pAkt signaling pathway may provide a novel prognostic marker and therapeutic target for non–small cell lung cancer.