title: Neuropilin-1 promotes epithelial-to-mesenchymal transition by stimulating nuclear factor-kappa B and is associated with poor prognosis in human oral squamous cell carcinoma.
abstract: BACKGROUND
  The epithelial-to-mesenchymal transition (EMT) is a key process in carcinogenesis, invasion, and metastasis of oral squamous cell carcinoma (OSCC). In our previous studies, we found that neuropilin-1 (NRP1) is overexpressed in tongue squamous cell carcinoma and that this overexpression is associated with cell migration and invasion. Nuclear factor-kappa B (NF-κB) plays an essential role both in the induction and the maintenance of EMT and tumor metastasis. Therefore, we hypothesized that NRP1 induces EMT, and that NRP1-induced migration and invasion may be an important mechanism for promoting invasion and metastasis of OSCC through NF-κB activation.
  
  
  RESULTS
  The variations in gene and protein expression and the changes in the biological behavior of OSCC cell lines transfected with a vector encoding NRP1, or the corresponding vector control, were evaluated. NRP1 overexpression promoted EMT and was associated with enhanced invasive and metastatic properties. Furthermore, the induction of EMT promoted the acquisition of some cancer stem cell (CSC)-like characteristics in OSCC cells. We addressed whether selective inhibition of NF-κB suppresses the NRP1-mediated EMT by treating cells with pyrrolidinedithiocarbamate ammonium (PDTC), an inhibitor of NF-κB. Immunohistochemical analysis of NRP1 in OSCC tissue samples further supported a key mediator role for NRP1 in tumor progression, lymph node metastasis, and indicated that NRP1 is a predictor for poor prognosis in OSCC patients.
  
  
  CONCLUSIONS
  Our results indicate that NRP1 may regulate the EMT process in OSCC cell lines through NF-κB activation, and that higher NRP1 expression levels are associated with lymph node metastasis and poor prognosis in OSCC patients. Further investigation of the role of NRP1 in tumorigenesis may help identify novel targets for the prevention and therapy of oral cancers.
authors.affiliation: Institute of Stomatology, Nanjing Medical University, Nanjing, PR China; Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Chu
authors.affiliation: Institute of Stomatology, Nanjing Medical University, Nanjing, PR China; Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
authors.forename: Xueming
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Stomatology, Nanjing Medical University, Nanjing, PR China; Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Ma
authors.affiliation: Institute of Stomatology, Nanjing Medical University, Nanjing, PR China; Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Institute of Stomatology, Nanjing Medical University, Nanjing, PR China; Department of Basic Science of Stomatology, College of Stomatology, Nanjing Medical University, Nanjing, PR China.
authors.forename: Mengying
authors.initials: M
authors.lastname: He
authors.affiliation: Institute of Stomatology, Nanjing Medical University, Nanjing, PR China.
authors.forename: Zilu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Stomatology, Nanjing Medical University, Nanjing, PR China; Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
authors.forename: Yunong
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D012333:RNA, Messenger; D039942:Neuropilin-1; D002945:Cisplatin