Team 1 - Liver Cancer and Tumor Invasion

Team 1 results from the gathering of scientists with the aim of performing both fundamental and translational research in the field of liver carcinogenesis.

Team leaders

Violaine MOREAU, DR2 INSERM
violaine.moreau@inserm.fr
+33 (0)5 57 57 12 72

Frédéric SALTEL, DR2 INSERM
frederic.saltel@inserm.fr
+33 (0)5 57 57 17 07

Research description

Hepatocellular carcinoma (HCC) is the major type of primary liver cancer. It is the 6th most frequent cancer worldwide and the 2nd leading cause of cancer-related death. The overall poor prognosis of HCC is due to high rates of postoperative recurrence and metastasis incidence. Intrahepatic metastases, including satellite nodules and venous metastases, are hallmark features of HCC progression.

Cellular migration and invasion through tissue barriers is key in the dissemination of cancer cells during metastasis.
The aim of our research is to unravel the mechanisms that are implicated in tumor cell migration and invasion.

Our main research axes:

Mediators of liver carcinogenesis (beta-catenin, RhoGTPases, translation factors)
Molecular bases of tumor invasion (Invadosomes, Type I Collagen, discoidin domain receptors, RhoGTPases)
Translational research on liver tumors

Publications

2022

Sala M, Allain N, Moreau M, Jabouille A., Henriet E, Abou Hammoud A, Uguen A, Di-Tommaso S, Dourthe C, Raymond AA, Dupuy JW, Gerard E, Senant N, Rousseau B, Merlio JP, Pham Ledart A, Vergier B, Tartare-Deckert S, Moreau V, Saltel F. Discoidin Domain Receptor 2 orchestrates melanoma resistance combining phenotype switching and proliferation. Oncogene, 2022, Accepted.
Basbous S, Paysan L, Sena S, Allain N, Hiriart JB, Dugot-Senant N, Rousseau B, Chevret E, Lagrée V, Moreau V. Silencing of Rnd3/RhoE inhibits the growth of human hepatocellular carcinoma and is associated with reversible senescence. Cancer Gene Therapy, 2022, Accepted.
Julien C, Le Bail B, Balabaud C, Bioulac-Sage P. Risk factors for bleeding hepatocellular adenoma. Liver Int. 2022 Feb 7. doi: 10.1111/liv.15184.
Decraecker M, Dutartre D, Hiriart JB, Irles-Depé M, Chermak F, Foucher J, de Lédinghen V. Long-term prognosis of patients with metabolic (dysfunction)-associated fatty liver disease by non-invasive methods.Aliment Pharmacol Ther. 2022 Mar;55(5):580-592.

2021

Karatas E, Raymond AA, Leon C, Dupuy JW, Di-Tommaso S, Senant N, Collardeau-Frachon S, Ruiz M, Lachaux A, Saltel F, Bouchecareilh M. JHep Reports. 3(4):100297 (2021).
Dourthe, C., C. Julien, S. Di Tommaso, J.-W. Dupuy, N. Dugot-Senant, A. Brochard, B. Le Bail, J.-F. Blanc, L. Chiche, C. Balabaud, P. Bioulac-Sage, F. Saltel, and A.-A. Raymond. Proteomic Profiling of Hepatocellular Adenomas Paves the Way to Diagnostic and Prognostic Approaches. Hepatology. 74:1595–1610 (2021). doi:10.1002/hep.31826.
Javary J, Allain N, Ezzoukhry Z, Di Tommaso S, Dupuy J-W, Dugot-Senant N, Costet P, Saltel F, Moreau V, Dubus P, Benhamouche-Trouillet S. Reptin/RUVBL2 is required for hepatocyte proliferation in vivo, liver regeneration and homeostasis. Liver International, 2021 Jun;41(6):1423-1429.
Cassinotto C, Boursier J, Paisant A, Guiu B, Irles-Depe M, Canivet C, Aube C, de Ledinghen V. Transient Versus Two-Dimensional Shear-Wave Elastography in a Multistep Strategy to Detect Advanced Fibrosis in NAFLD.Hepatology. 2021 Jun;73(6):2196-2205.
Sempoux C, Gouw ASH, Dunet V, Paradis V, Balabaud C, Bioulac-Sage P. Predictive Patterns of Glutamine Synthetase Immunohistochemical Staining in CTNNB1-mutated Hepatocellular Adenomas. Am J Surg Pathol. 2021 Apr 1;45(4):477-487.
Cappellen D, Catry-Thomas I, Castain C, Bioulac-Sage P. Hepatocellular adenoma with a double mutation HNF1A and IDH1 in a patient with Ollier disease. Liver Int. 2021 Dec;41(12):3009-3010.
Decraecker M, Toulouse C, Blanc JF. Is There Still a Place for Tyrosine Kinase Inhibitors for the Treatment of Hepatocellular Carcinoma at the Time of Immunotherapies? A Focus on Lenvatinib.Cancers (Basel). 2021 Dec 16;13(24):6310.
Joly P, Ruiz M, Garin R, Karatas E, Lachaux A, Restier L, Belmalih A, Renoux C, Lombard C, Dechomet M, Bouchecareilh M. A Particular SORL1 Micro-haplotype May Prevent Severe Liver Disease in a French Cohort of Alpha 1-Antitrypsin-deficient Children. J Pediatr Gastroenterol Nutr. 2021 Sep 1;73(3):e68-e72.
Karatas E, Bouchecareilh M. Alpha 1-Antitrypsin deficiency in liver explants in a Mexican cohort: A unique cohort to assess the role of heterozygous genotypes in liver disease. Clin Res Hepatol Gastroenterol. 2021 May;45(3):101538.
Leon C, Bouchecareilh M. The Autophagy Pathway: A Critical Route in the Disposal of Alpha 1-Antitrypsin Aggregates That Holds Many Mysteries.Int J Mol Sci. 2021 Feb 13;22(4):1875.

2020

M. Ros, A. T. Nguyen, J. Chia, S. Le Tran, X. Le Guezennec, R. McDowall, S. Vakhurshev, H. Clausen, M. Humphries, F. Saltel, F. A. Bard, ER-resident oxidoreductases surface to promote matrix degradation and tumor invasiveness, Nature Cell Biology. 2020 Nov;22(11):1371-1381. doi: 10.1038/s41556-020-00590-w.
Bouvet F, Ros M, Bonedeau E, Croissant C, Frelin L, Saltel F, Moreau V, Bouter A. Defective membrane repair machinery impairs survival of invasive cancer cells. Scientific reports, 2020.
Karatas E, Bouchecareilh M. Alpha 1-Antitrypsin Deficiency: A Disorder of Proteostasis-Mediated Protein Folding and Trafficking Pathways. Int J Mol Sci. 2020 Feb 21;21(4):1493.
Basbous S, Azzarelli R, Pacary E, Moreau V. Pathophysiological functions of Rnd proteins. Small GTPases. 2020 Oct 15;1-22.
M. Sala, D. Gonzales, T. Leste-Lasserre, N. Dugot-Senant, V. Paradis, S. Di Tommaso, J.-W. Dupuy, V. Pitard, C. Dourthe, A. Sciarra, C. Sempoux, L. D. Ferrell, A. D. Clouston, G. Miller, M. M. Yeh, S. Thung, A. S. H. Gouw, A. Quaglia, J. Han, J. Huan, C. Fan, J. Crawford, Y. Nakanuma, K. Harada, B. le Bail, C. Castain, N. Frulio, H. Trillaud, L. Possenti, J.-F. Blanc, L. Chiche, C. Laurent, C. Balabaud, P. Bioulac-Sage, A. A. Raymond, F. Saltel, ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice, Hepatology Communications, 2020, 4, 809–824.

2019

Di Martino J, Mascalchi P, Legros P, Lacomme S, Gontier E, Bioulac-Sage P, Balabaud C, Moreau V, Saltel F. Actin depolymerization in dedifferentiated liver sinusoidal endothelial cells promotes fenestrae re-formation. Hepatology Communications, 2019, 3, 213–219.
Héraud C, Pinault M, Lagrée V, Moreau V. p190RhoGAPs, the ARHGAP35- and ARHGAP5-encoded proteins, in health and disease. Cells, 2019 Apr 12;8(4).
Ruiz M, Lacaille F, Berthiller J, Joly P, Dumortier J, Aumar M, Bridoux-Henno L, Jacquemin E, Lamireau T, Broué P, Rivet C, Belmalih A, Restier L, Chapuis-Cellier C, Bouchecareilh M, Lachaux A; Groupe Francophone d’Hépatologie Gastroentérologie et Nutrition Pédiatriques. Liver disease related to alpha1-antitrypsin deficiency in French children: The DEFI-ALPHA cohort. Liver Int. 2019 Jun;39(6):1136-1146.

2018

Piquet L, Robbe T, Neaud V, Basbous S, Rosciglione S, Saltel F, Moreau V. Rnd3/RhoE expression is regulated by G-actin through MKL1-SRF activity. Exp Cell Res, 2018 Sep 15;370(2):227-236.
Ezzoukhry Z#, Henriet E#, Cordelières FP, Dupuy JW, Maître M, Gay N, Di-Tommaso S, Mercier L, Goetz JG, Peter M, Bard F, Moreau V, Raymond AA* and Saltel F*§. Combining laser capture micro-dissection and proteomics reveals an active translation machinery controlling invadosome formation. Nature Communications, 2018 May 23;9(1):2031.
Di Martino J, Mascalchi P, Legros P, Lacomme S, Gontier E, Bioulac-Sage P, Balabaud C, Moreau V and Saltel F. STED microscopy: a simplified method for liver sinusoidal endothelial fenestrae analysis. Biology of the Cell, 2018 Jul;110(7):159-168.
Henriet E, Sala M, Hammoud AA, Tuariihionoa A, Martino JD, Ros M, Saltel F. Multitasking discoidin domain receptors are involved in several and specific hallmarks of cancer. Cell Adh Migr. 2018 Apr 27:1-28. doi: 10.1080/19336918.2018.1465156. PMID:29701112
Croissant C, Tuariihionoa A, Bacou M, Souleyreau W, Sala M, Henriet E, Bikvalvi A, Saltel F, Auguste P. DDR1 and DDR2 physical interaction leads to signaling interconnection but with possible distinct functions. Cell Adh Migr. 2018 Apr 4:0. doi:10.1080/19336918.2018.1460012. [Epub ahead of print] PMID:29616590
Balabaud C, Laurent C, Le Bail B, Castain C, Possenti L, Frulio N, Chiche L, Blanc JF, Bioulac-Sage P. Unexpected discovery of small HNF1α-inactivated hepatocellular adenoma in pathological specimens from patients resected for liver tumours. Liver Int. 2018 Jul;38(7):1273-1279.
Javary J, Allain-Courtois N, Saucisse N, Costet P, Heraud C, Benhamed F, Pierre R, Bure C, Pallares-Lupon N, Do Cruzeiro M, Postic C, Cota D, Dubus P, Rosenbaum J, Benhamouche-Trouillet S. Liver Reptin/RUVBL2 controls glucose and lipid metabolism with opposite actions on mTORC1 and mTORC2 signalling. Gut 2018 Dec;67(12):2192-2203.

2017

Joly P, Lachaux A, Ruiz M, Restier L, Belmalih A, Chapuis-Cellier C, Francina A, Renoux C, Bouchecareilh M. SERPINA1 and MAN1B1 polymorphisms are not linked to severe liver disease in a French cohort of alpha-1 antitrypsin deficiency children.Liver Int. 2017 Nov;37(11):1608-1611. doi: 10.1111/liv.13586.
Raymond AA, Javary J, Breig O, Neaud V, Rosenbaum J. Reptin regulates insulin-stimulated Akt phosphorylation in hepatocellular carcinoma via the regulation of SHP-1/PTPN6.Cell Biochem Funct. 2017 Aug;35(6):289-295. doi: 10.1002/cbf.3274. Epub 2017 Aug 22
Henriet E, Hammoud AA, Dupuy JW, Dartigues B, Ezzoukry Z, Dugot-Senant N, Leste-Lasserre T, Pallares-Lupon N, Nikolski M, Le Bail B, Blanc JF, Balabaud C, Bioulac-Sage P, Raymond AA, Saltel F. Argininosuccinate synthase 1 (ASS1): A marker of unclassified hepatocellular adenoma and high bleeding risk. Hepatology. 2017 Jun 23;. [Epub ahead of print]
Joly P, Vignaud H, Di Martino J, Ruiz M, Garin R, Restier L, Belmalih A, Marchal C, Cullin C, Arveiler B, Fergelot P, Gitler AD, Lachaux A, Couthouis J, Bouchecareilh M. ERAD defects and the HFE-H63D variant are associated with increased risk of liver damages in Alpha 1-Antitrypsin Deficiency. PLoS One. 2017 Jun 15;12(6):e0179369.
Saltel F, Giese A, Azzi L, Elatmani H, Costet P, Ezzoukhry Z, Dugot-Senant N, Miquerol L, Boussadia O, Wodrich H, Dubus P, Jacquemin-Sablon H. Unr defines a novel class of nucleoplasmic reticulum, involved in mRNA translation. J Cell Sci, 2017 Apr 6. pii: jcs.198697. doi: 10.1242/jcs.198697
Di Martino J*, Henriet E*, Ezzoukhry Z, Mondal C, Bravo-Cordero J, Moreau V, Saltel F. 2D and 3D matrices to study linear invadosome formation and activity. J. Vis. Exp., e54911, doi:10.3791/54911 *equal contribution
Bidaud-Meynard A, Binamé F, Lagree V, Moreau V. Regulation of Rho GTPase activity at the leading edge of migrating cells by p190RhoGAP. SmallGTPases, 2017 Mar 13:1-12. (Review).
Breig O, Yates M, Neaud V, Couchy G, Grigoletto A, Lucchesi C, Prox J, Zucman-Rossi J, Becker-Pauly C, Rosenbaum J. Metalloproteinase meprin α regulates migration and invasion of human hepatocarcinoma cells and is a mediator of the oncoprotein Reptin. Oncotarget. 2017 Jan 31;8(5):7839-7851.

Main publications before 2017

Ezzoukhry Z*, Henriet E*, Piquet L, Boyé K, Bioulac-Sage P, Balabaud C, Zucman-Rossi J, Moreau V, Saltel F. TGF-b1 promotes linear invadosome formation in hepatocellular carcinoma cells, through DDR1 up-regulation and collagen I cross-linking. Eur J Cell Biol, 2016 Nov;95(11):503-512.
Paysan L*, Piquet L*, Saltel F, Moreau V. Rnd3 in Cancer: a Review of the Evidence for Tumor Promoter or Suppressor. Mol Cancer Res, 2016 Nov;14(11):1033-1044. *equal contribution
Binamé F*, Bidaud-Meynard A*, Magnan L, Piquet L, Montibus B, Chabadel A, Saltel F, Lagree V, Moreau V. Cancer-associated mutations in the protrusion-targeting region of p190RhoGAP impact tumor cell migration. J Cell Biol, 2016 Sep 26;214(7):859-73. *equal contribution
Di Martino J*, Henriet E*, Ezzoukhry Z*, Goetz J, Moreau V, Saltel F. The microenvironment controls invadosome plasticity. J Cell Sci, 2016, 1;129(9):1759-68. (Review) *equal contribution
Moreau V, Cordelières FP, Poujol C, Sagot I, Saltel F. Meeting report – Imaging The Cell. J Cell Sci, 2015, 128(21):3843-7. (Meeting Report)
Raymond AA, Benhamouche S, Neaud V, Di Martino J, Javary J, Rosenbaum J. Reptin regulates DNA double strand breaks repair in human hepatocellular carcinoma. PLoS One. 2015 Apr 15;10(4):e0123333.
Di Martino J, Moreau V, Saltel F. Type I collagen fibrils: an inducer of invadosomes. Oncotarget, 2015, 6(30):28519-20. (Editorial)
Juin A*, Di Martino J*, Leitinger B, Henriet E, Gary AS, Paysan L, Bomo J, Baffet G, Gauthier-Rouvière C, Rosenbaum J, Moreau V# and Saltel F#. Discoidin domain receptor 1 controls linear invadosome formation via a Cdc42/Tuba pathway. * equal contribution, # co-corresponding. J Cell Biol, 2014, 207(4):517-33.
Di Martino J*, Paysan L*, Gest C*, Lagrée V, Juin A, Saltel F# and Moreau V#. Cdc42 and Tks5: a minimal and universal molecular signature for functional invadosomes. Cell Adh Migr, 2014, Apr 16;8(3). *,#equal contribution.
Juin A, Planus E, Guillemot F, Horakova P, Albiges-Rizo C, Génot E, Rosenbaum J, Moreau V, Saltel F. Extracellular matrix rigidity controls podosome induction in microvascular endothelial cells. Biol Cell. 2013 Jan;105(1):46-57.
Bidaud-Meynard A*, Arma D*, Taouji S*, Laguerre M, Dessolin J, Rosenbaum J, Chevet E#, Moreau V#. A novel small-molecule screening strategy identifies mitoxantrone as a RhoGTPase inhibitor. Biochem J, 2013 Feb 15;450(1):55-62. *,# equal contribution
Grigoletto A, Neaud V, Allain-Courtois N, Lestienne P, Rosenbaum J. The ATPase activity of Reptin is required for its effects on tumor cell growth and viability in hepatocellular carcinoma. Mol Cancer Res, 2013, 11(2): 133–9.
Dejeans N, Pluquet O, Lhomond S, Grise F, Bouchecareilh M, Juin A, Meynard-Cadars M, Bidaud-Meynard PA, Gentil C, Moreau V, Saltel F, Chevet E. Autocrine control of glioma cells adhesion/migration through Inositol Requiring enzyme 1a (IRE1a)-mediated cleavage of Secreted Protein Acidic Rich in Cysteine (SPARC) mRNA. J Cell Sci, 2012, 125(Pt 18):4278-87.
Grise F, Sena S, Bidaud-Meynard A, Baud J, Hiriart JB, Makki K, Dugot-Senant N, Staedel C, Bioulac-Sage P, Zucman-Rossi J, Rosenbaum J, Moreau V. Rnd3/RhoE is down-regulated in hepatocellular carcinoma and controls cellular invasion. Hepatology, 2012, 55, 1766-1775. *equal contribution.
Juin A, Billottet C*, Moreau V*, Destaing O, Albiges-Rizo C, Rosenbaum J, Génot E#, Saltel F#. Physiological type I collagen organization induces the formation of a novel class of linear invadosomes. Mol Biol Cell 2012, 23(2):297-309.

Our Covers

Team members

member	status	affiliation
ALLAIN Nathalie	Technician	University of Bordeaux
BALABAUD Charles	Pr Emeritus	University of Bordeaux
BASBOUS Sara	Post-doc	University of Bordeaux
BILLOTTET Clotilde	Assistant Professor	University of Bordeaux
BIOULAC-SAGE Paulette	Pr Emeritus	University of Bordeaux
BLANC Jean-Frédéric	PU-PH	University Hospital of Bordeaux
BONNARD Benjamin	Post-doc	INSERM
BOUCHECAREILH Marion	CRCN CNRS	CNRS
DANTZER Camille	PhD Student	University of Bordeaux
DELAMARRE Adèle	PhD Student
DE LEDINGHEN Victor	PU-PH	University Hospital of Bordeaux
DIF Lydia	PhD Student	University of Bordeaux
DI TOMMASO Sylvaine	Engineer (CDD)	Ast Innovations
DOURTHE Cyril	Engineer (CDD)	Inserm
HERAUD Capucine	PhD student	University of Bordeaux
JABOUILLE Arnaud	Post-doc	INSERM (CDD Fondation de France)
LAGRÉE-BRINGTOWN Valérie	Assistant Professor	University of Bordeaux
LE BAIL Brigitte	PU-PH	University Hospital of Bordeaux
LEHMANN Alexandra	PhD Student	INSERM
LEON Céline	Engineer	University of Bordeaux
MOREAU Mélanie	PhD student	University of Bordeaux
MOREAU Violaine	DR2 INSERM	INSERM
NEAUD Véronique	Technician	University of Bordeaux
NORMAND Léa	PhD student	University of Bordeaux
PINAULT Mathilde	PhD student	University of Bordeaux
RAYMOND Anne-Aurélie	Engineer (IR)	INSERM
ROUYER Lucile	Engineer	INSERM
SALTEL Frédéric	DR2 INSERM	INSERM