Centre de Référence Maladies Rares


Biotherapy of genetic diseases, inflammatory disorders and cancers (BMGIC)

FR: Biologie Fondamentale Appliquée à la Médecine

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MIRCADE team (Methods and Innovations for Research in Pediatric Cancers)
Project 5.1

Liver: pediatric (hepatoblastoma) and adult (hepatocellular carcinoma)

keywords: hepatoblastoma, hepatocellular carcinoma, Immuno-oncology, beta-catenine, metabolic adaptation


In this area of research, we have two main themes:

  • a.beta-catenin regulation, new oncogenic pathways and miRNA alterations in liver cancer.

Principal Investigator : C.F. Grosset, PhD, Inserm DR2
Workgroup members : P. Veschambre, PhD, Assist. Prof.; N. Mosca, PhD, Post-doc; A. Ghousein, PhD student.
Our interests consist in understanding the regulation of beta-catenin (CTNNB1), that control Wnt signaling, normal and pathological cell gene reprogramming, embryonic tissue development and tumorigenesis. Using RNA-seq technology, we are also looking at characterizing new pathway alterations (eg. Fanconi Anemia) and at identifying new molecular signatures (ex. TOP2A) specific of the aggressive and chemoresistant form of hepatoblastoma. Finally, we are investigating in details the role of miRNA:targets interaction network in liver carcinogenesis and tumor molecular signaling using integrative bioinformatics and state-of-the-art in vitro/in vivo techniques.

The accepted version of our last article is available here: Liver Int. Ghousein A, 2019

  • b. Immuno-oncology and metabolic adaptation.

Principal Investigator : A. Merched, PhD, Prof.
Workgroup members : V. Trezeguet-Busquet, PhD, CNRS CR1; M. Alannan, PhD student.
Our aim is to characterize the immunosuppressive mechanisms in the tumor microenvironment and the changes in lipid metabolism associated with tumorigenesis by combining molecular, cellular and in vivo approaches.

Related publications:

  • DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases. Khoubai, F.Z. and Grosset, C.F. Int. J. Mol. Sci. () doi: doi.org/10.3390/ijms2221115
  • Deciphering Tumour Tissue Organization by 3D Electron Microscopy and machine learning. Denis de Senneville, B§, Khoubai, F.Z§, Bevilacqua, M., Labedade, A., Flosseau, K., Chardot, C., Branchereau, S., Ripoche, J., Cairo, S.*, Gontier, E.* and Grosset, C.F.* §These two authors contributed equally. *These three authors co-supervised the work. Communications Biology () doi: 10.1101/2021.06.15.446847
  • Targeting Lipid Metabolism in Liver Cancer. Alannan M, Fayyad-Kazan H, Trézéguet V, Merched A. Biochemistry () doi: 10.1021/acs.biochem.0c00477
  • miR-4510 blocks hepatocellular carcinoma development through RAF1 targeting and RAS/RAF/MEK/ERK signaling inactivation. A Ghousein, N Mosca, F Cartier, J Charpentier, J-W Dupuy, A-A Raymond, P Bioulac-Sage and CF Grosset Liver International () Accepted for publication.
  • Tracking cellular and molecular changes in a species-specific manner during experimental hepatoblastoma progression in vivo Indersie E#, Hooks KB#, Capdevielle C, Fabre M, Dugot-Senant N, Desplat A, Lepreux S, Merched A, Grosset CF, Hagedorn M. # contributed equally Oncotarget () 10.18632/oncotarget.24598
  • Role of O-glycanation and convertase maturation of the soluble Glypican-3 in inhibiting proliferation of hepatocellular carcinoma cells Saad A, Liet B, Joucla G, Santarelli X, Charpentier J, Claverol S, Grosset CF, Trézéguet V. Biochemistry () 10.1021/acs.biochem.7b01208
  • New insights into diagnosis and therapeutic options for proliferative hepatoblastoma. Hooks KB, Audoux J, Fazli H, Lesjean S, Ernault T, Senant ND, Leste-Lasserre T, Hagedorn M, Rousseau B, Danet C, Branchereau S, Brugières L, Taque S, Guettier C, Fabre M, Rullier A, Buendia MA, Commes T, Grosset CF*, Raymond AA*. * co-last authors. Hepatology () 10.1002/hep.29672
  • SimBA: A methodology and tools for evaluating the performance of RNA-Seq bioinformatic pipelines. Audoux J, Salson M, Grosset CF, Beaumeunier S, Holder JM, Commes T, Philippe N. BMC Bioinformatics () PMC5623974
  • New tumor suppressor microRNAs target glypican-3 in human liver cancer. Cartier F, Indersie E, Lesjean S, Charpentier J, Hooks KB, Ghousein A, Desplat A, Dugot-Senant N, Trézéguet V, Sagliocco F, Hagedorn M, Grosset CF. Oncotarget () PMC5522324
  • MicroRNA Therapy Inhibits Hepatoblastoma Growth In Vivo by Targeting b -Catenin and Wnt Signaling Emilie Indersie, Sarah Lesjean, Katarzyna B. Hooks , Francis Sagliocco, Tony Ernault, Stefano Cairo, Maria Merched-Sauvage, Anne Rullier, Brigitte Le Bail, Sophie Taque, Michael Grotzer, Sophie Branchereau, Catherine Guettier, Monique Fabre, Laurence Brugières, Martin Hagedorn, Marie-Annick Buendia, and Christophe F. Grosset Hepatology Communications () onlinelibrary.wiley.com/doi/10.1
  • MicroRNA-1291-mediated silencing of IRE1α enhances Glypican-3 expression. Maurel M, Dejeans N, Taouji S, Chevet E, Grosset CF. RNA () PMC3683912
  • A functional screening identifies five microRNAs controlling glypican-3: role of miR-1271 down-regulation in hepatocellular carcinoma. Maurel M, Jalvy S, Ladeiro Y, Combe C, Vachet L, Sagliocco F, Bioulac-Sage P, Pitard V, Jacquemin-Sablon H, Zucman-Rossi J, Laloo B, Grosset CF. Hepatology () janv 2013 PMID : 22865282
  • Molecular basis of differential target regulation by miR-96 and miR-182: the Glypican-3 as a model. Jalvy-Delvaille S, Maurel M, Majo V, Pierre N, Chabas S, Combe C, Rosenbaum J, Sagliocco F, Grosset CF. Nucleic Acids Res () fev 2012. PMID: 22009679

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