EphB3 Is Overexpressed in Non-Small-Cell Lung Cancer and Promotes Tumor Metastasis by Enhancing Cell Survival and Migration

• Published in: Cancer research (Chicago, Ill.) Vol. 71; no. 3; pp. 1156 - 1166
• Main Authors: JI, Xiao-Dan, GUO LI, KOEFFLER, H. Phillip, TONG, Xiang-Jun, DONG XIE, FENG, Yu-Xiong, ZHAO, Jiang-Sha, LI, Jing-Jing, SUN, Zhi-Jian, SHUO SHI, DENG, Yue-Zhen, XU, Jun-Feng, ZHU, Yin-Qiu
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.02.2011
• Subjects: Animals; Antineoplastic agents; Apoptosis - physiology; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - enzymology; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Caspase 8 - metabolism; Cell Adhesion - physiology; Cell Growth Processes - physiology; Cell Line, Tumor; Cell Movement - physiology; Cell Survival - physiology; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Disease Progression; DNA, Neoplasm - biosynthesis; DNA, Neoplasm - genetics; Gene Knockdown Techniques; Humans; Lung Neoplasms - enzymology; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical sciences; Mice; Mice, Nude; Neoplasm Metastasis; Pharmacology. Drug treatments; Pneumology; Receptor, EphB3 - biosynthesis; Receptor, EphB3 - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumors; Tumors of the respiratory system and mediastinum; Lung disease; Cell motility; Cell survival; Respiratory disease; Lung cancer; Gene overexpression; Bronchus disease; Metastasis; Malignant tumor; non-small cell lung carcinoma; Cell migration; Cancer
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-10-0717

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.