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Blockade of four-transmembrane L6 family member 5 (TM4SF5)-mediated tumorigenicity in hepatocytes by a synthetic chalcone derivative

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dc.contributor.authorLee, Jung Weon-
dc.contributor.authorLee, Sin-Ae-
dc.contributor.authorRyu, Hyung Won-
dc.contributor.authorKim, Young Mee-
dc.contributor.authorChoi, Suyong-
dc.contributor.authorLee, Mi Ji-
dc.contributor.authorKwak, Tae Kyoung-
dc.contributor.authorKim, Hyeon Jung-
dc.contributor.authorCho, Moonjae-
dc.contributor.authorPark, Ki Hun-
dc.date.accessioned2009-05-12T23:55:31Z-
dc.date.available2009-05-12T23:55:31Z-
dc.date.issued2009-
dc.identifier.citationHEPATOLOGY 2009;49:1316-1325.en
dc.identifier.issn0270-9139-
dc.identifier.urihttp://hdl.handle.net/10371/3226-
dc.description.abstractWe previously reported that the four-transmembrane L6 family member 5 (TM4SF5) was highly expressed in hepatocarcinoma, induced morphological elongation and epithelial-mesenchymal transition, and caused abnormal cell growth in multilayers in vitro and tumor formation in vivo. In this study, we identified a synthetic compound, 4'-(p-toluenesulfonylamido)-4-hydroxychalcone (TSAHC) that antagonized both the TM4SF5-mediated multilayer growth and TM4SF5-enhanced migration/invasion. TSAHC treatment induced multilayer-growing cells to grow in monolayers, recovering contact inhibition without accompanying apoptosis, and inhibited chemotactic migration and invasion. Tumor formation in nude mice injected with TM4SF5-expressing cells and the growth of cells expressing endogenous TM4SF5, but not of TM4SF5-null cells, was suppressed by treatment with TSAHC, but not by treatment with its analogs. The structure-activity relationship indicated the significance of 4'-p-toluenesulfonylamido and 4-hydroxy groups for the anti-TM4SF5 effects of TSAHC. Point mutations of the putative N-glycosylation sites abolished the TM4SF5-specific TSAHC responsiveness. CONCLUSION: These observations suggest that TM4SF5-enhanced tumorigenic proliferation and metastatic potential can be blocked by TSAHC, likely through targeting the extracellular region of TM4SF5, which is important for protein-protein interactions.en
dc.language.isoen-
dc.publisherJohn Wiley & Sonsen
dc.subjectTSAHCen
dc.subjectTM4SF5en
dc.subjectanti-canceren
dc.subjectdrugen
dc.titleBlockade of four-transmembrane L6 family member 5 (TM4SF5)-mediated tumorigenicity in hepatocytes by a synthetic chalcone derivativeen
dc.typeArticleen
dc.contributor.AlternativeAuthor이정원-
dc.contributor.AlternativeAuthor이신애-
dc.contributor.AlternativeAuthor류형원-
dc.contributor.AlternativeAuthor최수용-
dc.contributor.AlternativeAuthor이미지-
dc.contributor.AlternativeAuthor곽태경-
dc.contributor.AlternativeAuthor김현정-
dc.contributor.AlternativeAuthor조문재-
dc.contributor.AlternativeAuthor박기훈-
dc.identifier.doi10.1002/hep.22777-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Journal Papers (저널논문_의학과)
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