Original publications

 

Precision medicine for hepatocelluar carcinoma using molecular pattern diagnostics: results from a preclinical pilot study.

Agarwal R, Cao Y, Hoffmeier K, Krezdorn N, Jost L, Meisel AR, Jüngling R, Dituri F, Mancarella S, Rotter B, Winter P, Giannelli G.

Cell Death Dis. 2017 Jun 8;8(6):e2867. doi: 10.1038/cddis.2017.229.

NGS-based transcriptome profiling reveals biomarkers for companion diagnostics of the TGF-β receptor blocker galunisertib in HCC.

Cao Y, Agarwal R, Dituri F, Lupo L, Trerotoli P, Mancarella S, Winter P, Giannelli G.

Cell Death Dis. 2017 Feb 23;8(2):e2634. doi: 10.1038/cddis.2017.44.

Transforming Growth Factor-β Drives the Transendothelial Migration of Hepatocellular Carcinoma Cells.

Koudelkova P, Costina V, Weber G, Dooley S, Findeisen P, Winter P, Agarwal R, Schlangen K, Mikulits W.

Int J Mol Sci. 2017 Oct 10;18(10). pii: E2119. doi: 10.3390/ijms18102119.

The level of caveolin-1 expression determines response to TGF-β as a tumour suppressor in hepatocellular carcinoma cells.

Moreno-Càceres J, Caballero-Díaz D, Nwosu ZC, Meyer C, López-Luque J, Malfettone A, Lastra R, Serrano T, Ramos E, Dooley S, Fabregat I.
Cell Death Dis. 2017 Oct 12;8(10):e3098. doi: 10.1038/cddis.2017.469.

Role of the Transforming Growth Factor-β in regulating hepatocellular carcinoma oxidative metabolism.

Soukupova J, Malfettone A, Hyroššová P, Hernández-Alvarez MI, Peñuelas-Haro I, Bertran E, Junza A, Capellades J, Giannelli G, Yanes O, Zorzano A, Perales JC, Fabregat I.
Sci Rep. 2017 Oct 2;7(1):12486. doi: 10.1038/s41598-017-12837-y.

Hybrid polymeric-protein nano-carriers (HPPNC) for targeted delivery of TGFβ inhibitors to hepatocellular carcinoma cells.

Hanafy NAN, Quarta A, Di Corato R, Dini L, Nobile C, Tasco V, Carallo S, Cascione M, Malfettone A, Soukupova J, Rinaldi R, Fabregat I, Leporatti S.
J Mater Sci Mater Med. 2017 Aug;28(8):120. doi: 10.1007/s10856-017-5930-7. Epub 2017 Jul 6.

Transforming growth factor-β-induced plasticity causes a migratory stemness phenotype in hepatocellular carcinoma.

Malfettone A, Soukupova J, Bertran E, Crosas-Molist E, Lastra R, Fernando J, Koudelkova P, Rani B, Fabra Á, Serrano T, Ramos E, Mikulits W, Giannelli G, Fabregat I.
Cancer Lett. 2017 Apr 28;392:39-50. doi: 10.1016/j.canlet.2017.01.037. Epub 2017 Feb 2.

Snail mediates crosstalk between TGFβ and LXRα in hepatocellular carcinoma.

Bellomo C, Caja L, Fabregat I, Mikulits W, Kardassis D, Heldin CH, Moustakas A.
Cell Death Differ. 2017 Dec 11. doi: 10.1038/s41418-017-0021-3. [Epub ahead of print]

Somatic Ephrin Receptor Mutations Are Associated with Metastasis in Primary Colorectal Cancer.

Mathot L, Kundu S, Ljungström V, Svedlund J, Moens L, Adlerteg T, Falk-Sörqvist E, Rendo V, Bellomo C, Mayrhofer M, Cortina C, Sundström M, Micke P, Botling J, Isaksson A, Moustakas A, Batlle E, Birgisson H, Glimelius B, Nilsson M, Sjöblom T.
Cancer Res. 2017 Apr 1;77(7):1730-1740. doi: 10.1158/0008-5472.CAN-16-1921. Epub 2017 Jan 20.

Chemical regulators of epithelial plasticity reveal a nuclear receptor pathway controlling myofibroblast differentiation.

Carthy JM, Stöter M, Bellomo C, Vanlandewijck M, Heldin A, Morén A, Kardassis D, Gahman TC, Shiau AK, Bickle M, Zerial M, Heldin CH, Moustakas A.
Sci Rep. 2016 Jul 19;6:29868. doi: 10.1038/srep29868

BMP-9 interferes with liver regeneration and promotes liver fibrosis.

Breitkopf-Heinlein K, Meyer C, König C, Gaitantzi H, Addante A, Thomas M, Wiercinska E, Cai C, Li Q, Wan F, Hellerbrand C, Valous NA, Hahnel M, Ehlting C, Bode JG, Müller-Bohl S, Klingmüller U, Altenöder J, Ilkavets I, Goumans MJ, Hawinkels LJ, Lee SJ, Wieland M, Mogler C, Ebert MP, Herrera B, Augustin H, Sánchez A, Dooley S, Ten Dijke P.
Gut. 2017 May;66(5):939-954. doi: 10.1136/gutjnl-2016-313314. Epub 2017 Mar 23.

Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis.

Soukupova J, Bertran E, Peñuelas-Haro I, Urdiroz-Urricelqui U, Borgman M, Kohlhof H, Fabregat I.

Oncotarget. 2017 Nov 30;8(66):110367-110379. doi: 10.18632/oncotarget.22775. eCollection 2017 Dec 15.

Comparative analysis of TGF-β/Smad signaling dependent cytostasis in human hepatocellular carcinoma cell lines.

Dzieran J, Fabian J, Feng T, Coulouarn C, Ilkavets I, Kyselova A, Breuhahn K, Dooley S, Meindl-Beink
PLoS One. 2013 Aug 22;8(8):e72252. doi: 10.1371/journal.pone.0072252. Erratum in: PLoS One. 2014;9(5):e95952.

Bone morphogenetic protein-9 induces epithelial to mesenchymal transition in hepatocellular carcinoma cells.
Li Q, Gu X, Weng H, Ghafoory S, Liu Y, Feng T, Dzieran J, Li L, Ilkavets I, Kruithof-de Julio M, Munker S, Marx A, Piiper A, Augusto Alonso E, Gretz N, Gao C, Wölfl S, Dooley S, Breitkopf-Heinlein K.
Cancer Sci. 2013 Mar;104(3):398-408. doi: 10.1111/cas.12093.

Differential Inhibition of the TGF-β Signaling Pathway in HCC Cells Using the Small Molecule Inhibitor LY2157299 and the D10 Monoclonal Antibody against TGF-β Receptor Type II.
Dituri F, Mazzocca A, Fernando J, Papappicco P, Fabregat I, De Santis F, Paradiso A, Sabbà C, Giannelli G.
PLoS One. 2013 Jun 27;8(6):e67109. doi: 10.1371/journal.pone.0067109. Erratum in: PLoS One. 2013;8(7). doi:10.1371/annotation/c943a596-3965-4a5b-a27c-55c16685ea32. Peidrò, Fernando Juan [corrected to Fernando, Joan]. PLoS One. 2014;9(6):e100604.

Transforming growth factor-β (TGF-β)-mediated connective tissue growth factor (CTGF) expression in hepatic stellate cells requires Stat3 signaling activation.
Liu Y, Liu H, Meyer C, Li J, Nadalin S, Königsrainer A, Weng H, Dooley S, ten Dijke P.
J Biol Chem. 2013 Oct 18;288(42):30708-19. doi: 10.1074/jbc.M113.478685

Caveolin-1 is required for TGF-β-induced transactivation of the EGF receptor pathway in hepatocytes through the activation of the metalloprotease TACE/ADAM17.

J. Moreno-Càceres, L. Caja, J. Mainez, R. Mayoral, P. Martín-Sanz, R. Moreno-Vicente, M.A. Del Pozo, S. Dooley, G. Egea, I. Fabregat
Cell Death Dis. 2014 Jul 17;5:e1326. doi: 10.1038/cddis.2014.294.

BMP9-Induced Survival Effect in Liver Tumor Cells Requires p38MAPK Activation.

García-Álvaro M Addante A, Roncero C, Fernández M,Fabregat I, Sánchez A, Herrera B.
Int J Mol Sci. 2015 Aug 28;16(9):20431-48.  

HGF/c-Met signaling promotes liver progenitor cell migration and invasion by an epithelial-mesenchymal transition-independent, phosphatidyl inositol-3 kinase-dependent pathway in an in vitro model. 

Suárez-Causado A, Caballero-Díaz D, Bertrán E, Roncero C, Addante A, García-Álvaro M, Fernández M, Herrera B, Porras A,Fabregat I, Sánchez A.
Biochim Biophys Acta. 2015 Oct;1853(10 Pt A):2453-63.
 

Liver Sinusoidal Endothelial Cells Escape Senescence by Loss of p19ARF


Koudelkova, P., Weber, G., and Mikulits, W  . (2015).
PLoS One10:e0142134. 

Smad7 regulates compensatory hepatocyte proliferation in damaged mouse liver and positively relates to better clinical outcome in human hepatocellular carcinoma.

T. Feng, J. Dzieran, X. Gu, S. Marhenke, A. Vogel, K. Machida, T.S. Weiss, P. Rümmele, O. Kollmar, P. Hoffmann, F. Graesser, H. Allgayer, J. Fabian, H. Weng, A. Teufel, T. Maass, C. Meyer, U. Lehmann, C. Zhu, P.R. Mertens, C.F. Gao, S. Dooley, N.M. Meindl-Beinker. 
Clinical Science (Lond). 2015;128:761-774. 

A mesenchymal-like phenotype and expression of CD44 predict lack of apoptotic response to sorafenib in liver tumor cells. 

Fernando J, Malfettone A, Cepeda EB, Vilarrasa-Blasi R, Bertran E, Raimondi G, Fabra À, Alvarez-Barrientos A, Fernández-Salguero P, Fernández-Rodríguez CM, Giannelli G, Sancho P,Fabregat I. 

Int J Cancer. 2015 Feb 15;136(4):E161-72. doi: 10.1002/ijc.29097. Epub 2014 Aug 4. 

Multicenter analysis of soluble Axl reveals diagnostic value for very early stage hepatocellular carcinoma.

P. Reichl, M. Fang, P. Starlinger, K. Staufer, R. Nenutil, P. Muller, K. Greplova, D. Valik, S. Dooley, C. Brostjan, T. Gruenberger, J. Shen, K. Man, M. Trauner, J. Yu, C.F. Gao, W. Mikulits.
Int J Cancer. 2015 Jul 15;137(2):385-94. doi: 10.1002/ijc.29394.
 

Dissecting the role of epidermal growth factor receptor catalytic activity during liver regeneration and hepatocarcinogenesis.

López-Luque J, Caballero-Díaz D, Martinez-Palacián A, Roncero C, Moreno-Càceres J, García-Bravo M, Grueso E, Fernández A, Crosas-Molist E, García-Álvaro M, Addante A, Bertran E, Valverde AM, González-Rodríguez Á, Herrera B, Montoliu L, Serrano T, Segovia JC, Fernández M, Ramos E, Sánchez A,Fabregat I. Hepatology. 2016 Feb;63(2):604-19. doi: 10.1002/hep.28134. Epub 2015 Oct 10.

Chemical regulators of epithelial plasticity reveal a nuclear receptor pathway controlling myofibroblast differentiation.

Carthy JM, Stöter M, Bellomo C; Vanlandewijck M, Heldin A, Morén A, Kardassis D, Gahman TC, Shiau AK, Bickle M, Zerial M, Heldin CH, Moustakas A.
Sci Rep. 2016 Jul 19;6:29868. doi: 10.1038/srep29868. 

TGF-β1 and TGF-β2 abundance in liver diseases of mice and men. 

Dropmann A, Dediulia T, Breitkopf-Heinlein K, Korhonen H, Janicot M, Weber SN, Thomas M, Piiper A, Bertran E, Fabregat I, Abshagen K, Hess J, Angel P, Coulouarn C, Dooley S, Meindl-Beinker NM.
Oncotarget. 2016 Apr 12;7(15):19499-518. doi: 10.18632/oncotarget.6967.

Delta-Like Ligand 4 Modulates Liver Damage by Down-Regulating Chemokine Expression.

 

Shen Z, Liu Y, Dewidar B, Hu J, Park O, Feng T, Xu C, Yu C, Li Q, Meyer C, Ilkavets I, Müller A, Stump-Guthier C, Munker S, Liebe R, Zimmer V, Lammert F, Mertens PR, Li H, Ten Dijke P, Augustin HG, Li J, Gao B, Ebert MP, Dooley S, Li Y, Weng HL. 

Am J Pathol. 2016 Jul;186(7):1874-89. doi: 10.1016/j.ajpath.2016.03.010.

Transforming Growth Factor β1 (TGF-β1) Activates Hepcidin mRNA Expression in Hepatocytes.

Chen S, Feng T, Maja VS, Altamura S, Breitkopf-Heinlein K, Altenoder J, Weiss TS, Dooley S, Muckenthaler MU.
J Biol Chem. 2016 Jun 17;291(25):13160-74. doi: 10.1074/jbc.M115.691543. 

Inhibition of TGFβ type I receptor activity facilitates liver regeneration upon acute CCl4 intoxication in mice.

S. Karkampouna, M.J. Goumans, P. Ten Dijke, S. Dooley, M. Kruithof-de Julio.
Arch Toxicol. 2016 Feb;90(2):347-57

Caveolin-1-dependent activation of the metalloprotease TACE/ADAM17 by TGF-β in hepatocytes requires activation of Src and the NADPH oxidase NOX1.
Moreno-Càceres J, Mainez J, Mayoral R, Martín-Sanz P, Egea G, Fabregat I.
FEBS J. 2016 Apr;283(7):1300-10. doi: 10.1111/febs.13669

Laminin-332 sustains chemoresistance and quiescence as part of the human hepatic cancer stem cell niche.

Govaere, O.,Wouters, J.,Petz, M. ,Vandewynckel, Y.P.,Van den Eynde, K. ,Van den Broeck, A.,Verhulst, S .,Dollé, L.,Gremeaux, L .,Ceulemans, A .,Nevens,F.,van Grunsven, L.A .,Topal, B .,Vankelecom, H ,Giannelli, G .,Van Vlierberghe, H.,Mikulits, W,Komuta, M ., andRoskams, T . (2016).
J. Hepatol.64, 609-617

Glypican-3 promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells through ERK signaling pathway.

Y. Wu, H. Liu, H. Weng, X. Zhang, P. Li, C.L. Fan, B. Li, P.L. Dong, L. Li, S. Dooley, H.G. Ding.
Int J Oncol. 2015 Mar;46(3):1275-85. doi: 10.3892/ijo.2015.2827.

Hepatocyte-specific Smad7 deletion accelerates DEN-induced HCC via activation of STAT3 signaling in mice

Nadja Meindl-Beinker, Teng Feng, Johanna Dzieran, Xiaodong Yuan, Thorsten Maass, Andreas Teufel, Silke Marhenke, Timo Gaiser, Felix Rückert, Ingo Kleiter, Stephan Kanzler, Matthias Ebert, Arndt Vogel, Peter ten Dijke, Steven Dooley, and Anne Dropmann
[Paper #ONCSIS-16-0205R], Oncogenesis, in press

The NADPH oxidase NOX4 represses epithelial to amoeboid transition and efficient tumour dissemination.

Eva Crosas-Molist, Esther Bertran, Irene Rodriguez-Hernandez, Cecilia Herraiz, Gaia Cantelli, Àngels Fabra, Victoria Sanz-Moreno, Isabel Fabregat.
Oncogene 2016 Dec 12. doi: 10.1038/onc.2016.454. [Epub ahead of print]