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Article: Notch1-Snail1-E-cadherin pathway in metastatic hepatocellular carcinoma

TitleNotch1-Snail1-E-cadherin pathway in metastatic hepatocellular carcinoma
Authors
KeywordsEMT
HCC
metastasis
notch signaling
Issue Date2012
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal Of Cancer, 2012, v. 131 n. 3, p. E163-E172 How to Cite?
AbstractNotch signaling, a critical pathway for tissue development, also contributes to tumorigenesis in many cancers, but its pathological function in liver cancer is not well defined. In our study, Notch1 expression and its clinicopathological parameters were evaluated in 82 human hepatocellular carcinoma (HCC) patients. Plasmid-based siNotch1 shRNA was transiently or stably transfected into metastatic HCC cells and subsequently evaluated for the effects on orthotopic liver tumor metastasis in a mouse model as well as the effects on downstream pathways. Aberrant high expression of Notch1 was significantly associated with metastatic disease parameters in HCC patients, such as tumor-node-metastasis Stages III-IV and tumor venous invasion. Knocking-down Notch1 reduced cell motility in vitro and orthotopic tumor metastasis from the liver to the lung in vivo in a mouse model. In metastatic HCC cells, abnormal expression of Notch1 was associated with increased expression of Snail1 and repressed expression of E-cadherin; the Notch1-Snail1-E-cadherin association can also be found in HCC patient tumors. Inhibition of Notch1 by shRNA abolished Snail1 expression, which further resulted in the re-establishment of repressed E-cadherin in metastatic HCC cells. Thus, abnormal Notch1 expression was strongly associated with HCC metastatic disease, which might be mediated through the Notch1-Snail1-E-cadherin pathway. Knock-down of Notch1 reversed HCC tumor metastasis in a mouse model. Therefore, these data suggest that effective targeting of Notch signaling might also inhibit tumor metastasis. Copyright © 2011 UICC.
Persistent Identifierhttp://hdl.handle.net/10722/143794
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong59195
General Research Fund of Hong KongHKU 777708M
Funding Information:

Grant sponsor: The Seed Funding Program for Basic Research of The University of Hong Kong; Grant number: 59195; Grant sponsor: General Research Fund of Hong Kong; Grant number: HKU 777708M

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorWang, XQen_HK
dc.contributor.authorZhang, Wen_HK
dc.contributor.authorLui, ELHen_HK
dc.contributor.authorZhu, Yen_HK
dc.contributor.authorLu, Pen_HK
dc.contributor.authorYu, Xen_HK
dc.contributor.authorSun, Jen_HK
dc.contributor.authorYang, Sen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2011-12-21T08:56:07Z-
dc.date.available2011-12-21T08:56:07Z-
dc.date.issued2012en_HK
dc.identifier.citationInternational Journal Of Cancer, 2012, v. 131 n. 3, p. E163-E172en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/143794-
dc.description.abstractNotch signaling, a critical pathway for tissue development, also contributes to tumorigenesis in many cancers, but its pathological function in liver cancer is not well defined. In our study, Notch1 expression and its clinicopathological parameters were evaluated in 82 human hepatocellular carcinoma (HCC) patients. Plasmid-based siNotch1 shRNA was transiently or stably transfected into metastatic HCC cells and subsequently evaluated for the effects on orthotopic liver tumor metastasis in a mouse model as well as the effects on downstream pathways. Aberrant high expression of Notch1 was significantly associated with metastatic disease parameters in HCC patients, such as tumor-node-metastasis Stages III-IV and tumor venous invasion. Knocking-down Notch1 reduced cell motility in vitro and orthotopic tumor metastasis from the liver to the lung in vivo in a mouse model. In metastatic HCC cells, abnormal expression of Notch1 was associated with increased expression of Snail1 and repressed expression of E-cadherin; the Notch1-Snail1-E-cadherin association can also be found in HCC patient tumors. Inhibition of Notch1 by shRNA abolished Snail1 expression, which further resulted in the re-establishment of repressed E-cadherin in metastatic HCC cells. Thus, abnormal Notch1 expression was strongly associated with HCC metastatic disease, which might be mediated through the Notch1-Snail1-E-cadherin pathway. Knock-down of Notch1 reversed HCC tumor metastasis in a mouse model. Therefore, these data suggest that effective targeting of Notch signaling might also inhibit tumor metastasis. Copyright © 2011 UICC.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_HK
dc.relation.ispartofInternational Journal of Canceren_HK
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc..en_US
dc.subjectEMTen_HK
dc.subjectHCCen_HK
dc.subjectmetastasisen_HK
dc.subjectnotch signalingen_HK
dc.titleNotch1-Snail1-E-cadherin pathway in metastatic hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=&spage=&epage=&date=2011&atitle=Notch1-Snail1-E-cadherin+pathway+in+metastatic+hepatocellular+carcinomaen_US
dc.identifier.emailWang, XQ: xqwang@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityWang, XQ=rp00507en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ijc.27336en_HK
dc.identifier.pmid22052196-
dc.identifier.scopuseid_2-s2.0-84861573132en_HK
dc.identifier.hkuros197803en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84861573132&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume131en_HK
dc.identifier.issue3en_HK
dc.identifier.spageE163en_HK
dc.identifier.epageE172en_HK
dc.identifier.isiWOS:000304440100001-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectImportance of DNA damage mediated S and G2 checkpoint as a protective mechanism in stem cells-
dc.identifier.scopusauthoridWang, XQ=17343159900en_HK
dc.identifier.scopusauthoridZhang, W=54682547900en_HK
dc.identifier.scopusauthoridLui, ELH=36865643400en_HK
dc.identifier.scopusauthoridZhu, Y=54682549700en_HK
dc.identifier.scopusauthoridLu, P=55041426400en_HK
dc.identifier.scopusauthoridYu, X=54682502200en_HK
dc.identifier.scopusauthoridSun, J=54682374500en_HK
dc.identifier.scopusauthoridYang, S=54682570500en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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