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Article: Atypical localization of membrane type 1-matrix metalloproteinase in the nucleus is associated with aggressive features of hepatocellular carcinoma

TitleAtypical localization of membrane type 1-matrix metalloproteinase in the nucleus is associated with aggressive features of hepatocellular carcinoma
Authors
KeywordsLiver cancer
MT1-MMP/MMP14
Issue Date2007
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0899-1987/
Citation
Molecular Carcinogenesis, 2007, v. 46 n. 3, p. 225-230 How to Cite?
AbstractMembrane type 1-matrix metalloproteinase (MT1-MMP) is a versatile proteinase and recent studies indicated it could be internalized. Our earlier study found that it is overexpressed in hepatocellular carcinoma (HCC) and could promote intrahepatic metastasis. The present study was conducted to examine its subcellular localization and its clinicopathological significance in HCC after curative partial hepatectomy. Localization of MT1-MMP in 101 pairs of HCCs and their adjacent liver tissues, and 8 normal liver tissues was examined by the immunohistochemical method. MT1-MMP protein was localized at membrane and cytoplasm of hepatocytes in the normal and tumor adjacent liver tissues. In contrast, the HCCs were highly heterogeneous with variable degrees of membrane, cytoplasmic, and even nuclear staining. Interestingly, patients with presence of nuclear MT1-MMP were associated with poor overall survival (log-rank test, P = 0.043) and large tumor size (>5 cm) (Fisher's exact test, P = O.031). Subcellular distribution was further demonstrated by Western blotting and immunofluorescence with Hep3B stable transfectant overexpressing MT1-MMP. Western blot analyses of subcellular fractions confirmed a differential partitioning of various post-translationally modified MT1-MMP in these fractions. Different antibodies corroborated the presence of MT1-MMP in the nuclear fraction. Concomitant nuclear presence of MMP2 with MT1-MMP further indicated its potential involvement in the nuclear functions. MT1-MMP co-localized with caveolin-1 at the perinuclear region, suggesting nuclear translocation of MT1-MMP via caveolae-mediated endocytosis. In summary, the association of nuclear MT1-MMP with aggressive tumor features including poor prognosis and large tumor expands its functional repertoire and further indicates a new functional role of MMPs within nuclei of tumor cells. © 2007 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/83510
ISSN
2015 Impact Factor: 4.722
2015 SCImago Journal Rankings: 1.393
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorIp, YCen_HK
dc.contributor.authorCheung, STen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-09-06T08:41:53Z-
dc.date.available2010-09-06T08:41:53Z-
dc.date.issued2007en_HK
dc.identifier.citationMolecular Carcinogenesis, 2007, v. 46 n. 3, p. 225-230en_HK
dc.identifier.issn0899-1987en_HK
dc.identifier.urihttp://hdl.handle.net/10722/83510-
dc.description.abstractMembrane type 1-matrix metalloproteinase (MT1-MMP) is a versatile proteinase and recent studies indicated it could be internalized. Our earlier study found that it is overexpressed in hepatocellular carcinoma (HCC) and could promote intrahepatic metastasis. The present study was conducted to examine its subcellular localization and its clinicopathological significance in HCC after curative partial hepatectomy. Localization of MT1-MMP in 101 pairs of HCCs and their adjacent liver tissues, and 8 normal liver tissues was examined by the immunohistochemical method. MT1-MMP protein was localized at membrane and cytoplasm of hepatocytes in the normal and tumor adjacent liver tissues. In contrast, the HCCs were highly heterogeneous with variable degrees of membrane, cytoplasmic, and even nuclear staining. Interestingly, patients with presence of nuclear MT1-MMP were associated with poor overall survival (log-rank test, P = 0.043) and large tumor size (>5 cm) (Fisher's exact test, P = O.031). Subcellular distribution was further demonstrated by Western blotting and immunofluorescence with Hep3B stable transfectant overexpressing MT1-MMP. Western blot analyses of subcellular fractions confirmed a differential partitioning of various post-translationally modified MT1-MMP in these fractions. Different antibodies corroborated the presence of MT1-MMP in the nuclear fraction. Concomitant nuclear presence of MMP2 with MT1-MMP further indicated its potential involvement in the nuclear functions. MT1-MMP co-localized with caveolin-1 at the perinuclear region, suggesting nuclear translocation of MT1-MMP via caveolae-mediated endocytosis. In summary, the association of nuclear MT1-MMP with aggressive tumor features including poor prognosis and large tumor expands its functional repertoire and further indicates a new functional role of MMPs within nuclei of tumor cells. © 2007 Wiley-Liss, Inc.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0899-1987/en_HK
dc.relation.ispartofMolecular Carcinogenesisen_HK
dc.rightsMolecular Carcinogenesis. Copyright © John Wiley & Sons, Inc.en_HK
dc.subjectLiver canceren_HK
dc.subjectMT1-MMP/MMP14en_HK
dc.titleAtypical localization of membrane type 1-matrix metalloproteinase in the nucleus is associated with aggressive features of hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0899-1987&volume=46&issue=3&spage=225&epage=230&date=2007&atitle=Atypical+localization+of+membrane+type+1-matrix+metalloproteinase+in+the+nucleus+is+associated+with+aggressive+features+of+hepatocellular+carcinomaen_HK
dc.identifier.emailCheung, ST: stcheung@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityCheung, ST=rp00457en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/mc.20270en_HK
dc.identifier.pmid17219425-
dc.identifier.scopuseid_2-s2.0-33947152499en_HK
dc.identifier.hkuros126250en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33947152499&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume46en_HK
dc.identifier.issue3en_HK
dc.identifier.spage225en_HK
dc.identifier.epage230en_HK
dc.identifier.isiWOS:000244597500007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridIp, YC=36943517300en_HK
dc.identifier.scopusauthoridCheung, ST=7202473497en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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