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Molecular Medicine - Hecht Laboratory

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2023   Antón-García P, Haghighi EB, Rose K, Vladimirov G, Boerries M, Hecht A. TGFβ1-Induced EMT in the MCF10A Mammary Epithelial Cell Line Model Is Executed Independently of SNAIL1 and ZEB1 but Relies on JUNB-Coordinated Transcriptional Regulation. Cancers (Basel). 2023 Jan 16;15(2):558. doi: 10.3390/cancers15020558. PMID: 36672507; PMCID: PMC9856774  
    Fröhlich J, Rose K, Hecht A. Transcriptional activity mediated by β-CATENIN and TCF/LEF family members is completely dispensable for survival and propagation of multiple human colorectal cancer cell lines. Sci Rep. 2023 Jan 6;13(1):287. doi: 10.1038/s41598-022-27261-0. PMID: 36609428; PMCID: PMC9822887.  
2022   Flum, M., Dicks, S., Teng, Y-H., Schrempp, M., Nyström, A., Boerries, M., Hecht, A. Canonical TGFβ signaling induces collective invasion in colorectal carcinogenesis through a Snail1- and Zeb1-independent partial EMT.
Oncogene 2022 Mar;41(10):1492-1506. doi: 10.1038/s41388-022-02190-4. Epub 2022 Jan 24. PMID: 35075245
 
2021   Frey, P., Devisme, A., Rose, K. Schrempp, M, Freihen, V, Andrieux, G, Boerries, M, Hecht, A, SMAD4 mutations do not preclude epithelial–mesenchymal transition in colorectal cancer. Oncogene (2021). 2021/12/03, SN 1476-5594, https://doi.org/10.1038/s41388-021-02128-2. PMID: 34857888  
2020   Wenzel J, Rose K, Haghighi EB, Lamprecht C, Rauen G, Freihen V, Kesselring R, Boerries M, Hecht A. Oncogene. Loss of the nuclear Wnt pathway effector TCF7L2 promotes migration and invasion of human colorectal cancer cells. Oncogene2020 May;39(19):3893-3909. doi: 10.1038/s41388-020-1259-7. Pubmed32203164  
   

Frey P, Devisme A, Schrempp M, Andrieux G, Boerries M, Hecht A. Canonical BMP Signaling Executes Epithelial-Mesenchymal Transition Downstream of SNAIL1. Cancers (Basel). 2020 Apr 21;12(4). pii: E1019. doi: 10.3390/cancers12041019. Pubmed32326239

 
    Freihen V, Rönsch K, Mastroianni J, Frey P, Rose K, Boerries M, Zeiser R, Busch H, Hecht A. SNAIL1 employs β-Catenin-LEF1 complexes to control colorectal cancer cell invasion and proliferation.Int J Cancer. 146 (8), 2229-2242 2020 Apr 15. doi: 10.1002/ijc.32644. Pubmed31463973  
2019   Beyes S, Andrieux G, Schrempp M, Aicher D, Wenzel J, Antón-García P, Boerries M, Hecht A. Genome-wide mapping of DNA-binding sites identifies stemness-related genes as directly repressed targets of SNAIL1 in colorectal cancer cells. Oncogene. 2019 Oct;38(40):6647-6661. doi: 10.1038/s41388-019-0905-4. Epub 2019 Aug 7. Pubmed31391555  
2017   Jägle S, Busch H, Freihen V, Beyes S, Schrempp M, Boerries M, Hecht A. SNAIL1-mediated downregulation of FOXA proteins facilitates the inactivation of transcriptional enhancer elements at key epithelial genes in colorectal cancer cells. PLoS Genet. 2017 Nov 20;13(11):e1007109. doi: 10.1371/journal.pgen.1007109. eCollection 2017 Nov. Pubmed29155818  
    Jägle S, Dertmann A, Schrempp M, Hecht A. ZEB1 is neither sufficient nor required for epithelial-mesenchymal transition in LS174T colorectal cancer cells. Biochem Biophys Res Commun. 2017 Jan 22;482(4):1226-1232. doi: 10.1016/j.bbrc.2016.12.017. Pubmed27923654  
2016   Schnappauf O, Beyes S, Dertmann A, Freihen V, Frey P, Jägle S, Rose K, Michoel T, Grosschedl R, Hecht A. Enhancer decommissioning by Snail1-induced competitive displacement of TCF7L2 and down-regulation of transcriptional activators results in EPHB2 silencing. Biochim Biophys Acta. 2016 Nov;1859(11):1353-1367. doi: 10.1016/j.bbagrm.2016.08.002. Epub 2016 Aug 5. Pubmed27504909  
2015   Benary U, Kofahl B, Hecht A, Wolf J. Mathematical modelling suggests a differential impact of β-transducin repeat-containing protein paralogues on Wnt/β-catenin signalling dynamics. FEBS J. 2015 Mar;282(6):1080-96. doi: 10.1111/febs.13204. Pubmed25601154  
    Rönsch K, Jägle S, Rose K, Seidl M, Baumgartner F, Freihen V, Yousaf A, Metzger E, Lassmann S, Schüle R, Zeiser R, Michoel T, Hecht A. SNAIL1 combines competitive displacement of ASCL2 and epigenetic mechanisms to rapidly silence the EPHB3 tumor suppressor in colorectal cancer. Mol Oncol. 2015 Feb;9(2):335-54. doi: 10.1016/j.molonc.2014.08.016. Epub 2014 Sep 16. Pubmed25277775  
2014   Jägle S, Rönsch K, Timme S, Andrlová H, Bertrand M, Jäger M, Proske A, Schrempp M, Yousaf A, Michoel T, Zeiser R, Werner M, Lassmann S, Hecht A. Silencing of the EPHB3 tumor-suppressor gene in human colorectal cancer through decommissioning of a transcriptional enhancer. Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):4886-91. doi: 10.1073/pnas.1314523111. Epub 2014 Mar 18. Pubmed24707046  
2013   Elfert S, Weise A, Bruser K, Biniossek ML, Jägle S, Senghaas N, Hecht A. Acetylation of human TCF4 (TCF7L2) proteins attenuates inhibition by the HBP1 repressor and induces a conformational change in the TCF4::DNA complex. PLoS One. 2013 Apr 15;8(4):e61867. doi: 10.1371/journal.pone.0061867. Print 2013. Pubmed23613959  
    Benary U, Kofahl B, Hecht A, Wolf J. Modeling Wnt/β-Catenin Target Gene Expression in APC and Wnt Gradients Under Wild Type and Mutant Conditions. Front Physiol. 2013;4:21. doi: 10.3389/fphys.2013.00021. Epub 2013 Feb 25. Pubmed23508686  
2012   Wallmen B, Schrempp M, Hecht A.Intrinsic properties of Tcf1 and Tcf4 splice variants determine cell-type-specific Wnt/β-catenin target gene expression. Nucleic Acids Res. 2012 Oct 1;40(19):9455-69. doi: 10.1093/nar/gks690. Pubmed22859735  
2011   Rönsch K, Jäger M, Schöpflin A, Danciu M, Laßmann S, Hecht A. Class I and III HDACs and loss of active chromatin features contribute to epigenetic silencing of CDX1 and EPHB tumor suppressor genes in colorectal cancer. Epigenetics. 2011 May;6(5):610-22. Epub 2011 May 1. Pubmed21393996  
    Luckert K, Götschel F, Sorger PK, Hecht A, Joos TO, Pötz O. Snapshots of Protein Dynamics and Post-translational Modifications In One Experiment--{beta}-Catenin and Its Functions. Mol Cell Proteomics. 2011 May;10(5):M110.007377. Epub 2011 Mar 4. Pubmed21378377  
2010   Gebhardt R, Lerche KS, Götschel F, Günther R, Kolander J, Teich L, Zellmer S, Hofmann HJ, Eger K, Hecht A, Gaunitz F. 4-Amino-ethyl-amino-emodin - a novel potent inhibitor of GSK-3beta - acts as an insulin-sensitizer avoiding downstream effects of activated beta-catenin.J Cell Mol Med. 2010 Jun;14(6A):1276-93. Pubmed19228266  
    Weise A, Bruser K, Elfert S, Wallmen B, Wittel Y, Wöhrle S, Hecht A. Alternative splicing of Tcf7l2 transcripts generates protein variants with differential promoter-binding and transcriptional activation properties at Wnt/ß-catenin targets. Nucleic Acids Res. 2010 Apr;38(6):1964-81. Pubmed20044351  
2008   Denayer T, Locker M, Borday C, Deroo T, Janssens S, Hecht A, van Roy F, Perron M, Vleminckx K. Canonical Wnt signaling controls proliferation of retinal stem/progenitor cells in postembryonic Xenopus eyes. Stem Cells. 2008 Aug;26(8):2063-74. Pubmed18556512  
    Götschel F, Kern C, Lang S, Sparna T, Markmann C, Schwager J, McNelly S, von Weizsäcker F, Laufer S, Hecht A, Merfort I Inhibition of GSK3 differentially modulates NFκB, CREB, AP-1 and β-catenin signaling in hepatocytes, but fails to to promote TNF-α -induced apoptosis. Exp. Cell. Res. 2008 April 1; 314 (6): 1351-1366 Pubmed18261723  
2007   Wöhrle S, Wallmen B, Hecht A.:Differential control of Wnt target genes involves epigenetic mechanisms and selective promoter occupancy by TCFs. Mol Cell Biol. 2007 Dec;27(23):8164-8177 Pubmed17923689  
    Hirsch C, Campano LM, Wohrle S, Hecht A. Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures. Exp Cell Res. 2007 Feb 1;313(3):572-87. Pubmed17198701  
2006   Schepsky A, Bruser K, Gunnarsson GJ, Goodall J, Hallsson JH, Goding CR, Steingrimsson E, Hecht A. The microphthalmia-associated transcription factor Mitf interacts with beta-catenin to determine target gene expression. Mol Cell Biol. 2006 Dec;26(23):8914-27. Epub 2006 Sep 25. Pubmed17000761  
    Klingmuller U, Bauer A, Bohl S, Nickel PJ, Breitkopf K, Dooley S, Zellmer S, Kern C, Merfort I, Sparna T, Donauer J, Walz G, Geyer M, Kreutz C, Hermes M, Gotschel F, Hecht A, Walter D, Egger L, Neubert K, Borner C, Brulport M, Schormann W, Sauer C, Baumann F, Preiss R, MacNelly S, Godoy P, Wiercinska E, Ciuclan L, Edelmann J, Zeilinger K, Heinrich M, Zanger UM, Gebhardt R, Maiwald T, Heinrich R, Timmer J, von Weizsacker F, Hengstler JG. Primary mouse hepatocytes for systems biology approaches: a standardized in vitro system for modelling of signal transduction pathways. Syst Biol (Stevenage). 2006 Nov;153(6):433-47. Pubmed17186705  
    Kim S, Xu X, Hecht A, Boyer TG. Mediator is a transducer of Wnt/beta-catenin signaling. J Biol Chem. 2006 May 19;281(20):14066-75. Epub 2006 Mar 24. Pubmed16565090  
2005   Stemmler MP, Hecht A, Kemler R.  E-cadherin intron 2 contains cis-regulatory elements essential for gene expression. Development. 2005 Mar;132(5):965-76. Epub 2005 Jan 26. Pubmed15673570  
2004   Hecht A. Members of the T-cell factor family of DNA-binding proteins and their roles in tumorigenesis. in "Handbook of Experimental Pharmacology", Vol. 166, M. Gossen, J. Kaufmann und S. Triezenberg (eds.), Springer Verlag, Berlin, Heidelberg, 123-165  
2003   Shah S, Hecht A, Pestell R, Byers SW.  Trans-repression of beta-Catenin Activity by Nuclear Receptors. J Biol Chem. 2003 Nov 28;278(48):48137-48145. Epub 2003 Sep 12 Pubmed12972427  
    Stemmler MP, Hecht A, Kinzel B, Kemler R.  Analysis of regulatory elements of E-cadherin with reporter gene constructs in transgenic mouse embryos. Dev Dyn. 2003 Jun;227(2):238-45 Pubmed12761851  
    Hecht A, Stemmler MP.  Identification of a promoter-specific transcriptional activation domain at the C terminus of the Wnt effector protein T-cell factor 4.  J Biol Chem. 2003 Feb 7;278(6):3776-85. Epub 2002 Nov 22 Pubmed12446687  
2002   Hecht A, Stemmler MP. Identification of a promoter-specific transcriptional activation domain at the C-terminus of the Wnt-effector protein TCF4. J Biol Chem. 2003 Feb 7;278(6):3776-85. Epub 2002 Nov 22. Pubmed12446687  
    Aoki M, Sobek V, Maslyar DJ, Hecht A, Vogt PK. Oncogenic transformation by beta-catenin: deletion analysis and characterization of selected target genes. Oncogene 2002 Oct 10;21(46):6983-91 Pubmed12370820  
    Hecht A. Funktionen von ß-Catenin im Zellkern: Wie werden Zielgene des Wnt-Signalwegs reguliert? in Jahrbuch der Max-Planck-Gesellschaft 2002, MPG München, 190-194  
2000   Hecht A, Kemler R. Curbing the nuclear activities of beta-catenin. Control over Wnt target gene expression. EMBO Rep 2000 Jul;1(1):24-8 Pubmed11256619  
    Hecht A, Vleminckx K, Stemmler MP, van Roy F, Kemler R. The p300/CBP acetyltransferases function as transcriptional coactivators of beta-catenin in vertebrates. EMBO J 2000 Apr 17;19(8):1839-50 Pubmed10775268  
1999   Vogt PK, Aoki M, Bottoli I, Chang HW, Fu S, Hecht A, Iacovoni JS, Jiang BH, Kruse U. A random walk in oncogene space: the quest for targets. Cell Growth Differ 1999 Dec;10(12):777-84 Pubmed10616902  
    Hecht A, Grunstein M. Mapping DNA interaction sites of chromosomal proteins using immunoprecipitation and polymerase chain reaction. Methods Enzymol 1999;304:399-414 Pubmed10372373  
    Hecht A, Litterst CM, Huber O, Kemler R. Functional characterization of multiple transactivating elements in beta-catenin, some of which interact with the TATA-binding protein in vitro. J Biol Chem 1999 Jun 18;274(25):18017-25 Pubmed10364252  
    Hecht A, Strahl-Bolsinger S, Grunstein M. Mapping DNA interaction sites of chromosomal proteins. Crosslinking studies in yeast. Methods Mol Biol 1999;119:469-79 Pubmed10804533  
    Vleminckx K, Kemler R, Hecht A. The C-terminal transactivation domain of beta-catenin is necessary and sufficient for signaling by the LEF-1/beta-catenin complex in Xenopus laevis. Mech Dev 1999 Mar;81(1-2):65-74 Pubmed10330485  
    Aoki M, Hecht A, Kruse U, Kemler R, Vogt PK. Nuclear endpoint of Wnt signaling: neoplastic transformation induced by transactivating lymphoid-enhancing factor 1. Proc Natl Acad Sci U S A 1999 Jan 5;96(1):139-44 Pubmed9874785  
1997   Strahl-Bolsinger S, Hecht A, Luo K, Grunstein M. SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast. Genes Dev 1997 Jan 1;11(1):83-93 Pubmed9000052  
1996   Hecht A, Strahl-Bolsinger S, Grunstein M. Spreading of transcriptional repressor SIR3 from telomeric heterochromatin. Nature 1996 Sep 5;383(6595):92-6 Pubmed8779721  
1995   Grunstein M, Hecht A, Fisher-Adams G, Wan J, Mann RK, Strahl-Bolsinger S, Laroche T, Gasser S. The regulation of euchromatin and heterochromatin by histones in yeast. J Cell Sci Suppl 1995;19:29-36 Pubmed8655644  
    Hecht A, Laroche T, Strahl-Bolsinger S, Gasser SM, Grunstein M. Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast. Cell 1995 Feb 24;80(4):583-92 Pubmed7867066  
1993   Sippel AE, Schafer G, Faust N, Saueressig H, Hecht A, Bonifer C. Chromatin domains constitute regulatory units for the control of eukaryotic genes. Cold Spring Harb Symp Quant Biol 1993;58:37-44 Pubmed7956050  
    Thompson JS, Hecht A, Grunstein M. Histones and the regulation of heterochromatin in yeast. Cold Spring Harb Symp Quant Biol 1993;58:247-56 Pubmed7956035  
1992   Grewal T, Theisen M, Borgmeyer U, Grussenmeyer T, Rupp RA, Stief A, Qian F, Hecht A, Sippel AE. The -6.1-kilobase chicken lysozyme enhancer is a multifactorial complex containing several cell-type-specific elements. Mol Cell Biol 1992 May;12(5):2339-50 Pubmed1569954  
1991   Bonifer C, Hecht A, Saueressig H, Winter DM, Sippel AE. Dynamic chromatin: the regulatory domain organization of eukaryotic gene loci. J Cell Biochem 1991 Oct;47(2):99-108 Pubmed1757483  
    Sippel, A. E., Saueressig, H., Winter, D., Grewal, T., Faust, N., Hecht, A. und Bonifer, C. (1991), "The regulatory domain organization of eukaryotic genomes - implications for stable gene transfer.", in "Transgenic Mice in Biology and Medicine", F. Grosveld und G. Kollias (eds.), Acad. Press, London, 1-26.  
1989   Sippel, A. E., Stief, A., Hecht, A., Theisen, M., Borgmeyer, U., Rupp, R. A. W., Grewal, T. und Grussenmeyer, T. (1989), "The structural and functional domain organization of the chicken lysozyme gene locus.", in "Nucleic Acids and Molecular Biology 3", Eckstein, F. und Lilley, D. M. J. (eds.), Springer Verlag, Berlin Heidelberg, 133-147.  
1988   Bonifer, C., Hecht, A., Peters, C., and Sippel. A.E. (1988).  Rat antibodies as probes for the characterization of progesterone receptor A and B proteins from laying hen oviduct cytosol. Biochim. Biophys. Acta 968, 96-108 Pubmed3337848  
    Hecht A, Berkenstam A, Stromstedt PE, Gustafsson JA, Sippel AE. A progesterone responsive element maps to the far upstream steroid dependent DNase hypersensitive site of chicken lysozyme chromatin. EMBO J 1988 Jul;7(7):2063-73 Pubmed3416833  
    Sippel, A. E., Theisen, M., Borgmeyer, U., Strech-Jurk, U., Rupp, R. A. W., Püschel, A. W., Müller, A., Hecht, A., Stief, A. und Grussenmeyer, T. (1988), "Regulatory function and molecular structure of DNaseI hypersensitive elements in the chromatin domain of a gene.", in "Architecture of Eucaryotic Genes", G. Kahl (ed.) Verlagsgesellschaft Chemie (VHC), Weinheim, 355-369.  
       
       
       
       
       
       
       
       
       
       
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