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DLC-1 suppresses non-small cell lung cancer growth and invasion by RhoGAP-dependent and independent mechanisms
DC Field | Value | Language |
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dc.contributor.author | Healy, Kevin D. | - |
dc.contributor.author | Hodgson, Louis | - |
dc.contributor.author | Kim, Tai-Young | - |
dc.contributor.author | Shutes, Adam | - |
dc.contributor.author | Maddileti, Savitri | - |
dc.contributor.author | Juliano, Rudolph L. | - |
dc.contributor.author | Hahn, Klaus M. | - |
dc.contributor.author | Harden, T. Kendall | - |
dc.contributor.author | Bang, Yung-Jue | - |
dc.contributor.author | Der, Channing J. | - |
dc.date.accessioned | 2010-07-04T23:19:32Z | - |
dc.date.available | 2010-07-04T23:19:32Z | - |
dc.date.created | 2020-12-21 | - |
dc.date.issued | 2008-05 | - |
dc.identifier.citation | Molecular Carcinogenesis, Vol.47 No.5, pp.326-337 | - |
dc.identifier.issn | 0899-1987 | - |
dc.identifier.other | 119476 | - |
dc.identifier.uri | https://hdl.handle.net/10371/68196 | - |
dc.description.abstract | Expression of the tumor suppressor deleted in liver cancer-1 (DLC-1) is lost in non-small cell lung (NSCLC) and other human carcinomas, and ectopic DLC-1 expression dramatically reduces proliferation and tumorigenicity. DLC-1 is a multi-domain protein that includes a Rho GTPase activating protein (RhoGAP) domain which has been hypothesized to be the basis of its tumor suppressive actions. To address the importance of the RhoGAP function of DLC-1 in tumor suppression, we performed biochemical and biological studies evaluating DLC-1 in NSCLC. Full-length DLC-1 exhibited strong GAP activity for RhoA as well as RhoB and RhoC, but only very limited activity for Cdc42 in vitro. In contrast, the isolated RhoGAP domain showed 5- to 20-fold enhanced activity for RhoA, RhoB, RhoC, and Cdc42. DLC-1 protein expression was absent in six of nine NSCLC cell lines. Restoration of DLC-1 expression in DLC-1-deficient NSCLC cell lines reduced RhoA activity, and experiments with a RhoA biosensor demonstrated that DLC-1 dramatically reduces RhoA activity at the leading edge of cellular protrusions. Furthermore, DLC-1 expression in NSCLC cell lines impaired both anchorage-dependent and -independent growth, as well as invasion in vitro. Surprisingly, we found that the antitumor activity of DLC-1 was due to both RhoGAP-dependent and -independent activities. Unlike the rat homologue p122RhoGAP, DLC-1 was not capable of activating the phospholipid hydrolysis activity of phospholipase C-delta 1. Combined, these studies provide information on the mechanism of DLC-1 function and regulation, and further support the role of DLC-1 tumor suppression in NSCLC. (c) 2007 Wiley-Liss, Inc. | - |
dc.language | 영어 | - |
dc.language.iso | en | en |
dc.publisher | John Wiley & Sons Inc. | - |
dc.title | DLC-1 suppresses non-small cell lung cancer growth and invasion by RhoGAP-dependent and independent mechanisms | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 방영주 | - |
dc.identifier.doi | 10.1002/mc.20389 | - |
dc.citation.journaltitle | Molecular Carcinogenesis | - |
dc.identifier.wosid | 000255483200002 | - |
dc.identifier.scopusid | 2-s2.0-42949100728 | - |
dc.citation.endpage | 337 | - |
dc.citation.number | 5 | - |
dc.citation.startpage | 326 | - |
dc.citation.volume | 47 | - |
dc.identifier.sci | 000255483200002 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Bang, Yung-Jue | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | GTPASE-ACTIVATING PROTEIN | - |
dc.subject.keywordPlus | NUCLEOTIDE EXCHANGE FACTOR | - |
dc.subject.keywordPlus | HEPATOCELLULAR-CARCINOMA | - |
dc.subject.keywordPlus | BREAST-CARCINOMA | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | RHOA | - |
dc.subject.keywordPlus | TUMORIGENICITY | - |
dc.subject.keywordPlus | TRANSFORMATION | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | CDC42 | - |
dc.subject.keywordAuthor | GTPase activating protein | - |
dc.subject.keywordAuthor | Rho GTPases | - |
dc.subject.keywordAuthor | tumor suppressor | - |
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