Abstract
Eph receptors, the largest subfamily of transmembrane tyrosine kinase receptors, have been increasingly implicated in various physiologic and pathologic processes, and the roles of the Eph family members during tumorigenesis have recently attracted growing attention. Until now, research on EphB3 function in cancer is limited to focusing on tumor suppression by EphB receptors in colorectal cancer. However, its function in other types of cancer remains poorly investigated. In this study, we explored the function of EphB3 in non-small-cell lung cancer (NSCLC). We found that the expression of EphB3 was significantly upregulated in clinical samples and cell lines, and the expression level correlated with the patient pathologic characteristics, including tumor size, differentiation, and metastasis. Overexpression of EphB3 in NSCLC cell lines accelerated cell growth and migration and promoted tumorigenicity in xenografts in a kinase-independent manner. In contrast, downregulation of EphB3 inhibited cell proliferation and migration and suppressed in vivo tumor growth and metastasis. Furthermore, we showed that silencing of EphB3 inhibited cell growth by reducing DNA synthesis and caspase-8-mediated apoptosis and suppressed cell migration by increasing accumulation of focal adhesion formation. Taken together, our findings suggest that EphB3 provides critical support to the development and progression of NSCLC by stimulating cell growth, migration, and survival, thereby implicating EphB3 as a potential therapeutic target in NSCLC.
Highlights
Lung cancer is a major health challenge worldwide, ranking at one of the most common malignancies in the world
We showed that overexpression of EphB3 in non–small-cell lung cancer (NSCLC) cell lines accelerated cell growth and migration, as well as promoted tumorigenicity independent of its kinase activity, whereas knockdown of EphB3 showed the opposite effect, including inducing cell apoptosis and inhibiting tumor growth and metastasis in nude mice
We found that EphB3 was upregulated in NSCLC samples compared with their matched normal tissues
Summary
Lung cancer is a major health challenge worldwide, ranking at one of the most common malignancies in the world. In 2007, lung cancer accounted for 1.52 million cases or 12% of all newly diagnosed cancers [1]. Because of its poor prognosis, lung cancer was the leading cause of cancer deaths, causing 1.3 million deaths in 2007. The most common form of lung cancer is non–small-cell lung cancer (NSCLC), which comprises approximately 80% of all lung cancers. Overall 5year survival rate associated with NSCLC is a dismal 15%. NSCLC is divided into 3 types according to histologic char-
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