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Conference Paper: Nuclear targeted Deleted in liver cancer 1 exhibited reduced tumor suppressive function both in vitro and in vivo

TitleNuclear targeted Deleted in liver cancer 1 exhibited reduced tumor suppressive function both in vitro and in vivo
Authors
Issue Date2010
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
The 101st Annual Meeting of the American Association for Cancer Research (AACR), Washington DC., 17-21 April 2010. In Cancer Research, 2010, v. 70 n. 8 suppl., abstract no. 5007 How to Cite?
AbstractThe tumor suppressor Deleted in liver cancer 1 (DLC1) protects cell from transformation by catalyzing the GTP hydrolysis of active RhoA. Besides the RhoGAP activity, accumulating evidences have supported that localization at focal adhesions and interaction with tensin protein are key factors guiding the tumor suppressive activity of DLC1. In this study, we provided new evidence that DLC1 was a dynamic protein which shuttles between cytoplasm and nucleus instead of statically staying in the cytoplasm. Subcellular fractionation assay showed that DLC1 protein can be detected in cytoplasmic and nuclear fractions. Treatment of Leptomycin B (LMB), a nuclear export blocker, could lead to the nuclear retention of exogenous and endogenous DLC1 in different human cancer cell lines. Detail examination of relevant DLC1 mutants had shown that the center region of DLC1 was necessary and sufficient for its nuclear localization. We transiently expressed a NLS fusion DLC1 (NLS-DLC1) with preferential nuclear localization in SMMC HCC cells and found that NLS-DLC1 was less potent in suppressing colony formation and actin stress fiber formation. To study the tumor suppressive function of nuclear DLC1 both in vitro and in vivo, we employed retroviral transduction to stably express NLS-DLC1 in a p53−/− RasV12 hepatoblast model. We found that NLS-DLC1 expressing cells proliferated faster in vitro and exhibited increased tumorigenicity upon nude mice injection when compared with the non-nuclear targeted DLC1. Although the function of nuclear DLC1 remains to be answered, our results clearly demonstrated that nuclear localization of DLC1 may serve as a potential mechanism in negatively regulating its tumor suppressive activity.
DescriptionSession - Cellular and Molecular Biology: no. 5007
Persistent Identifierhttp://hdl.handle.net/10722/104827
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorChan, LK-
dc.contributor.authorKo, CF-
dc.contributor.authorNg, IOL-
dc.contributor.authorYam, JWP-
dc.date.accessioned2010-09-25T22:08:58Z-
dc.date.available2010-09-25T22:08:58Z-
dc.date.issued2010-
dc.identifier.citationThe 101st Annual Meeting of the American Association for Cancer Research (AACR), Washington DC., 17-21 April 2010. In Cancer Research, 2010, v. 70 n. 8 suppl., abstract no. 5007-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/104827-
dc.descriptionSession - Cellular and Molecular Biology: no. 5007-
dc.description.abstractThe tumor suppressor Deleted in liver cancer 1 (DLC1) protects cell from transformation by catalyzing the GTP hydrolysis of active RhoA. Besides the RhoGAP activity, accumulating evidences have supported that localization at focal adhesions and interaction with tensin protein are key factors guiding the tumor suppressive activity of DLC1. In this study, we provided new evidence that DLC1 was a dynamic protein which shuttles between cytoplasm and nucleus instead of statically staying in the cytoplasm. Subcellular fractionation assay showed that DLC1 protein can be detected in cytoplasmic and nuclear fractions. Treatment of Leptomycin B (LMB), a nuclear export blocker, could lead to the nuclear retention of exogenous and endogenous DLC1 in different human cancer cell lines. Detail examination of relevant DLC1 mutants had shown that the center region of DLC1 was necessary and sufficient for its nuclear localization. We transiently expressed a NLS fusion DLC1 (NLS-DLC1) with preferential nuclear localization in SMMC HCC cells and found that NLS-DLC1 was less potent in suppressing colony formation and actin stress fiber formation. To study the tumor suppressive function of nuclear DLC1 both in vitro and in vivo, we employed retroviral transduction to stably express NLS-DLC1 in a p53−/− RasV12 hepatoblast model. We found that NLS-DLC1 expressing cells proliferated faster in vitro and exhibited increased tumorigenicity upon nude mice injection when compared with the non-nuclear targeted DLC1. Although the function of nuclear DLC1 remains to be answered, our results clearly demonstrated that nuclear localization of DLC1 may serve as a potential mechanism in negatively regulating its tumor suppressive activity.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Research-
dc.titleNuclear targeted Deleted in liver cancer 1 exhibited reduced tumor suppressive function both in vitro and in vivo-
dc.typeConference_Paper-
dc.identifier.emailChan, LK: lokongchan@gmail.com-
dc.identifier.emailKo, CF: frankieko@pathology.hku.hk, bokcf@hkucc.hku.hk-
dc.identifier.emailNg, IOL: iolng@hkucc.hku.hk-
dc.identifier.emailYam, JWP: judyyam@pathology.hku.hk-
dc.identifier.authorityNg, IOL=rp00335-
dc.identifier.authorityYam, JWP=rp00468-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/1538-7445.AM10-5007-
dc.identifier.hkuros170192-
dc.identifier.volume70-
dc.identifier.issue8 suppl., abstract no. 5007-
dc.publisher.placeUnited States-

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