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Article: Neuropilin-2 promotes tumourigenicity and metastasis in oesophageal squamous cell carcinoma through ERK-MAPK-ETV4-MMP-E-cadherin deregulation

TitleNeuropilin-2 promotes tumourigenicity and metastasis in oesophageal squamous cell carcinoma through ERK-MAPK-ETV4-MMP-E-cadherin deregulation
Authors
KeywordsNRP2
ETV4
ESCC
RNA‐Seq
Metastasis
Issue Date2016
PublisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130
Citation
Journal of Pathology, 2016, v. 239 n. 3, p. 309-319 How to Cite?
AbstractOesophageal 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.
Persistent Identifierhttp://hdl.handle.net/10722/229690
ISSN
2019 Impact Factor: 5.979
2015 SCImago Journal Rankings: 4.176
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFung, TM-
dc.contributor.authorNg, KY-
dc.contributor.authorTong, M-
dc.contributor.authorChen, J-
dc.contributor.authorChai, S-
dc.contributor.authorChan, KT-
dc.contributor.authorLaw, S-
dc.contributor.authorLee, NP-
dc.contributor.authorChoi, MY-
dc.contributor.authorLi, B-
dc.contributor.authorCheung, AL-
dc.contributor.authorTsao, SW-
dc.contributor.authorQin, YR-
dc.contributor.authorGuan, X-
dc.contributor.authorChan, KW-
dc.contributor.authorMa, S-
dc.date.accessioned2016-08-23T14:12:41Z-
dc.date.available2016-08-23T14:12:41Z-
dc.date.issued2016-
dc.identifier.citationJournal of Pathology, 2016, v. 239 n. 3, p. 309-319-
dc.identifier.issn0022-3417-
dc.identifier.urihttp://hdl.handle.net/10722/229690-
dc.description.abstractOesophageal 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.-
dc.languageeng-
dc.publisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130-
dc.relation.ispartofJournal of Pathology-
dc.subjectNRP2-
dc.subjectETV4-
dc.subjectESCC-
dc.subjectRNA‐Seq-
dc.subjectMetastasis-
dc.titleNeuropilin-2 promotes tumourigenicity and metastasis in oesophageal squamous cell carcinoma through ERK-MAPK-ETV4-MMP-E-cadherin deregulation-
dc.typeArticle-
dc.identifier.emailFung, TM: ktmfung@hku.hk-
dc.identifier.emailNg, KY: jkyng@hku.hk-
dc.identifier.emailTong, M: caroltm@hku.hk-
dc.identifier.emailChai, S: stchai@HKUCC-COM.hku.hk-
dc.identifier.emailChan, KT: ktchan66@hku.hk-
dc.identifier.emailLaw, S: slaw@hkucc.hku.hk-
dc.identifier.emailLee, NP: nikkilee@hku.hk-
dc.identifier.emailLi, B: libinhku@hkucc.hku.hk-
dc.identifier.emailCheung, AL: lmcheung@hku.hk-
dc.identifier.emailTsao, SW: gswtsao@hku.hk-
dc.identifier.emailGuan, X: xyguan@hkucc.hku.hk-
dc.identifier.emailChan, KW: kwchan@pathology.hku.hk-
dc.identifier.emailMa, S: stefma@hku.hk-
dc.identifier.authorityTong, M=rp02568-
dc.identifier.authorityLaw, S=rp00437-
dc.identifier.authorityLee, NP=rp00263-
dc.identifier.authorityCheung, AL=rp00332-
dc.identifier.authorityTsao, SW=rp00399-
dc.identifier.authorityGuan, X=rp00454-
dc.identifier.authorityChan, KW=rp00330-
dc.identifier.authorityMa, S=rp00506-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/path.4728-
dc.identifier.pmid27063000-
dc.identifier.scopuseid_2-s2.0-85027929496-
dc.identifier.hkuros262347-
dc.identifier.volume239-
dc.identifier.issue3-
dc.identifier.spage309-
dc.identifier.epage319-
dc.identifier.isiWOS:000383594300007-
dc.publisher.placeUnited Kingdom-

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