title: Aberrant NRP-1 expression serves as predicator of metastatic endometrial and lung cancers.
abstract: 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.
authors.affiliation: Center for Molecular and Translational Medicine, Georgia State University, Atlanta, GA 30302, USA.
authors.forename: Imoh S
authors.initials: IS
authors.lastname: Okon
authors.affiliation: Center for Molecular and Translational Medicine, Georgia State University, Atlanta, GA 30302, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Section of Molecular Medicine, Oklahoma City, OK 73104, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Coughlan
authors.affiliation: Section of Molecular Medicine, Oklahoma City, OK 73104, USA.
authors.forename: Qiongxin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Center for Molecular and Translational Medicine, Georgia State University, Atlanta, GA 30302, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.affiliation: Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK 73104, USA.
authors.forename: Doris M
authors.initials: DM
authors.lastname: Benbrook
authors.affiliation: Center for Molecular and Translational Medicine, Georgia State University, Atlanta, GA 30302, USA.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zou
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D060787:Neoplasm Grading; D039942:Neuropilin-1 / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C099942:NEDD9 protein, human; D010750:Phosphoproteins; D039942:Neuropilin-1; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases
keywords: LKB1; NEDD9; NRP-1; endometrial and lung cancer; tumor metastases