Prognostic value of integrin ß1-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 beta 1 and beta 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 beta 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 beta 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 beta 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 beta 1-integrin-linked kinase-pAkt signaling pathway may provide a novel prognostic marker and therapeutic target for non-small cell lung cancer. (c) 2007 Elsevier Inc. All rights reserved.