000126504 001__ 126504
000126504 005__ 20240228140829.0
000126504 0247_ $$2doi$$a10.1042/CS20140606
000126504 0247_ $$2pmid$$apmid:25602745
000126504 0247_ $$2ISSN$$a0009-9287
000126504 0247_ $$2ISSN$$a0143-5221
000126504 0247_ $$2ISSN$$a0301-0538
000126504 0247_ $$2ISSN$$a1470-8736
000126504 0247_ $$2altmetric$$aaltmetric:3848536
000126504 037__ $$aDKFZ-2017-02532
000126504 041__ $$aeng
000126504 082__ $$a610
000126504 1001_ $$aFeng, Teng$$b0
000126504 245__ $$aSmad7 regulates compensatory hepatocyte proliferation in damaged mouse liver and positively relates to better clinical outcome in human hepatocellular carcinoma.
000126504 260__ $$aLondon$$bPortland$$c2015
000126504 3367_ $$2DRIVER$$aarticle
000126504 3367_ $$2DataCite$$aOutput Types/Journal article
000126504 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1523878965_1584
000126504 3367_ $$2BibTeX$$aARTICLE
000126504 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000126504 3367_ $$00$$2EndNote$$aJournal Article
000126504 520__ $$aTransforming growth factor β (TGF-β) is cytostatic towards damage-induced compensatory hepatocyte proliferation. This function is frequently lost during hepatocarcinogenesis, thereby switching the TGF-β role from tumour suppressor to tumour promoter. In the present study, we investigate Smad7 overexpression as a pathophysiological mechanism for cytostatic TGF-β inhibition in liver damage and hepatocellular carcinoma (HCC). Transgenic hepatocyte-specific Smad7 overexpression in damaged liver of fumarylacetoacetate hydrolase (FAH)-deficient mice increased compensatory proliferation of hepatocytes. Similarly, modulation of Smad7 expression changed the sensitivity of Huh7, FLC-4, HLE and HLF HCC cell lines for cytostatic TGF-β effects. In our cohort of 140 HCC patients, Smad7 transcripts were elevated in 41.4% of HCC samples as compared with adjacent tissue, with significant positive correlation to tumour size, whereas low Smad7 expression levels were significantly associated with worse clinical outcome. Univariate and multivariate analyses indicate Smad7 levels as an independent predictor for overall (P<0.001) and disease-free survival (P=0.0123). Delineating a mechanism for Smad7 transcriptional regulation in HCC, we identified cold-shock Y-box protein-1 (YB-1), a multifunctional transcription factor. YB-1 RNAi reduced TGF-β-induced and endogenous Smad7 expression in Huh7 and FLC-4 cells respectively. YB-1 and Smad7 mRNA expression levels correlated positively (P<0.0001). Furthermore, nuclear co-localization of Smad7 and YB-1 proteins was present in cancer cells of those patients. In summary, the present study provides a YB-1/Smad7-mediated mechanism that interferes with anti-proliferative/tumour-suppressive TGF-β actions in a subgroup of HCC cells that may facilitate aspects of tumour progression.
000126504 536__ $$0G:(DE-HGF)POF3-317$$a317 - Translational cancer research (POF3-317)$$cPOF3-317$$fPOF III$$x0
000126504 588__ $$aDataset connected to CrossRef, PubMed,
000126504 650_7 $$2NLM Chemicals$$aSmad7 Protein
000126504 650_7 $$2NLM Chemicals$$aTransforming Growth Factor beta
000126504 650_7 $$2NLM Chemicals$$aY-Box-Binding Protein 1
000126504 650_7 $$2NLM Chemicals$$aYBX1 protein, human
000126504 7001_ $$aDzieran, Johanna$$b1
000126504 7001_ $$aGu, Xing$$b2
000126504 7001_ $$aMarhenke, Silke$$b3
000126504 7001_ $$aVogel, Arndt$$b4
000126504 7001_ $$aMachida, Keigo$$b5
000126504 7001_ $$aWeiss, Thomas S$$b6
000126504 7001_ $$aRuemmele, Petra$$b7
000126504 7001_ $$aKollmar, Otto$$b8
000126504 7001_ $$aHoffmann, Patrick$$b9
000126504 7001_ $$aGrässer, Friedrich$$b10
000126504 7001_ $$0P:(DE-He78)69067807288b48415ceb4abc43b9ad54$$aAllgayer, Heike$$b11$$udkfz
000126504 7001_ $$aFabian, Jasmin$$b12
000126504 7001_ $$aWeng, Hong Lei$$b13
000126504 7001_ $$aTeufel, Andreas$$b14
000126504 7001_ $$aMaass, Thorsten$$b15
000126504 7001_ $$aMeyer, Christoph$$b16
000126504 7001_ $$aLehmann, Ulrich$$b17
000126504 7001_ $$aZhu, Cheng$$b18
000126504 7001_ $$aMertens, Peter R$$b19
000126504 7001_ $$aGao, Chun Fang$$b20
000126504 7001_ $$aDooley, Steven$$b21
000126504 7001_ $$aMeindl-Beinker, Nadja M$$b22
000126504 773__ $$0PERI:(DE-600)1484392-4$$a10.1042/CS20140606$$gVol. 128, no. 11, p. 761 - 774$$n11$$p761 - 774$$tClinical science$$v128$$x1470-8736$$y2015
000126504 909CO $$ooai:inrepo02.dkfz.de:126504$$pVDB
000126504 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)69067807288b48415ceb4abc43b9ad54$$aDeutsches Krebsforschungszentrum$$b11$$kDKFZ
000126504 9131_ $$0G:(DE-HGF)POF3-317$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vTranslational cancer research$$x0
000126504 9141_ $$y2015
000126504 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000126504 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000126504 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000126504 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCLIN SCI : 2015
000126504 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000126504 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000126504 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000126504 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000126504 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000126504 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000126504 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000126504 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000126504 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000126504 9201_ $$0I:(DE-He78)G360-20160331$$kG360$$lKKE Molekulare Onkologie solider Tumoren$$x0
000126504 980__ $$ajournal
000126504 980__ $$aVDB
000126504 980__ $$aI:(DE-He78)G360-20160331
000126504 980__ $$aUNRESTRICTED