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Neuropilin-2 promotes tumourigenicity and metastasis in oesophageal squamous cell carcinoma through ERK-MAPK-ETV4-MMP-E-cadherin deregulation
- Source :
- The Journal of Pathology. 239:309-319
- Publication Year :
- 2016
- Publisher :
- Wiley, 2016.
-
Abstract
- Oesophageal squamous cell carcinoma (ESCC) is the most common histological subtype of oesophageal cancer. The disease is particularly prevalent in southern China. The incidence of the disease is on the rise and its overall survival rate remains dismal. Identification and characterization of better molecular markers for early detection and therapeutic targeting are urgently needed. Here, we report levels of transmembrane and soluble neuropilin-2 (NRP2) to be significantly up-regulated in ESCC, and to correlate positively with advanced tumour stage, lymph node metastasis, less favourable R category and worse overall patient survival. NRP2 up-regulation in ESCC was in part a result of gene amplification at chromosome 2q. NRP2 overexpression promoted clonogenicity, angiogenesis and metastasis in ESCC in vitro, while NRP2 silencing by lentiviral knockdown or neutralizing antibody resulted in a contrary effect. This observation was extended in vivo in animal models of subcutaneous tumourigenicity and tail vein metastasis. Mechanistically, overexpression of NRP2 induced expression of ERK MAP kinase and the transcription factor ETV4, leading to enhanced MMP-2 and MMP-9 activity and, as a consequence, suppression of E-cadherin. In summary, NRP2 promotes tumourigenesis and metastasis in ESCC through deregulation of ERK-MAPK-ETV4-MMP-E-cadherin signalling. NRP2 represents a potential diagnostic or prognostic biomarker and therapeutic target for ESCC. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
- Subjects :
- 0301 basic medicine
Gene knockdown
Cadherin
Angiogenesis
Cancer
Biology
medicine.disease
medicine.disease_cause
Pathology and Forensic Medicine
Metastasis
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Downregulation and upregulation
030220 oncology & carcinogenesis
Cancer research
medicine
Gene silencing
Carcinogenesis
Subjects
Details
- ISSN :
- 00223417
- Volume :
- 239
- Database :
- OpenAIRE
- Journal :
- The Journal of Pathology
- Accession number :
- edsair.doi...........50a748b56609e93da96f5498a86cf31b