Prognostic value of integrin ß1-ILK-pAkt signaling pathway in non-small cell lung cancer
Prognostic value of integrin ß1-ILK-pAkt signaling pathway in non-small cell lung cancer
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DOI：
10.1016/j.humpath.2007.01.003
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发表时间：
2007-07-01
期刊：
影响因子：
3.3
通讯作者：
Ishigatsubo, Yoshiaki
中科院分区：
文献类型：
--
作者：
Okamura, Mayumi;Yamaji, Satoshi;Ishigatsubo, Yoshiaki
通过整合素-细胞外基质连接的细胞黏附信号对正常黏附细胞的生长和存活起着至关重要的作用。整合素连接蛋白是一种普遍表达的丝氨酸-苏氨酸蛋白激酶，能与整合素β1和β3的胞浆结构域相互作用，在整合素依赖的细胞黏附、扩散和细胞形态改变中发挥着整合素与细胞骨架之间的界面作用。在这项研究中，我们评估了1997年至2000年间连续118例手术切除的非小细胞肺癌组织中整合素β1、整合素连接的激酶和磷酸化Akt(Ser473；PACT)的表达。结果，我们在非小细胞肺癌组织标本中发现了整合素β1的强膜性染色、整合素连接的激酶的强细胞质染色和具有PACK颗粒的强细胞质染色的特定亚群。此外，我们提供的证据表明，整合素连接激酶、整合素β1和Akt的激活形式与非小细胞肺癌的不良预后相互关联，并且通过多因素分析，这些蛋白的同时过度表达是独立的预后因素(风险比，2.771；P=0.003)，可与T因素和淋巴侵袭等标准预后因素相媲美。因此，对整合素β1-整合素连接的激酶-PACT信号通路的进一步研究可能为非小细胞肺癌提供新的预后标记物和治疗靶点。(C)2007 Elsevier Inc.保留所有权利。
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.