Aberrant NRP-1 expression serves as predicator of metastatic endometrial and lung cancers
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Imoh S. Okon1, Ye Ding1, Kathleen A. Coughlan2, Qiongxin Wang2, Ping Song1, Doris M. Benbrook3, Ming-Hui Zou1
1Center for Molecular and Translational Medicine, Georgia State University, Atlanta, GA 30302, USA
2Section of Molecular Medicine, Oklahoma City, OK 73104, USA
3Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK 73104, USA
Imoh Okon, e-mail: [email protected]
Keywords: NRP-1, NEDD9, LKB1, tumor metastases, endometrial and lung cancer
Received: June 27, 2015 Accepted: November 25, 2015 Published: December 20, 2015
Neuropilin-1 (NRP-1) has emerged as an important driver of tumor-promoting phenotypes of human malignancies. However, incomplete knowledge exists as to how this single-pass transmembrane receptor mediates pleiotropic tumor-promoting functions. The purpose of this study was to evaluate NRP-1 expression and metastatic properties in 94 endometrial cancer and matching serum specimens and in a lung cancer cell line. We found that NRP-1 expression significantly correlated with increased tumoral expression of vascular endothelial growth factor 2 (VEGFR2) and serum levels of hepatocyte growth factor (HGF) and cell growth-stimulating factor (C-GSF). Tumoral NRP-1 also was positively associated with expression of NEDD9, a pro-metastatic protein. In the highly metastatic lung cancer cell line (H1792), stable LKB1 depletion caused increased migration in vitro and accentuated NRP-1 and NEDD9 expression in vivo. Our findings demonstrate that perturbed expression of these targets correlate with metastatic potential of endometrial and lung tumors, providing clinically-relevant biomarker applications for diagnostic and therapeutic targeting.
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