Team 03 - Liver Cancers and Tumor Invasion

Équipe 03 – Cancers du Foie et Invasion Tumorale

Team 3 results from the gathering of scientists with the aim of performing both fundamental and translational research on liver cancers.   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.   Three main research axes:

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

Keywords

liver cancer, invasion, actin cytoskeleton, extracellular matrix, proteostasis, proteomics, invadosomes, alpha 1-antitrypsin deficiency, translational reprogramming

News


Projects

1-Proteostasis in liver diseases (M. BOUCHECAREILH)

Dr Marion Bouchecareilh’s group aims to understand how proteostasis imbalances can lead to liver diseases such as Alpha 1-Antitrypsin Deficiency (AATD)-mediated liver disease and Hepatocellular Carcinoma (HCC).

•  AATD-Liver mediated liver disease: AATD is a rare genetic disease associated with liver injury (cholestasis, cirrhosis, HCC). The goal of our group is to identify factors involved in these liver injuries in order to use them as therapeutic targets and/or biomarkers.

•  eIF3-mediated translational reprogramming in HCC: eIF3 major complex of the translation machinery is composed of 13 non-identical protein subunits (eIF3a-m) most of which are dysregulated in many cancers including HCC. Our goal is to determine which eiF3 subunits are involved in carcinogenesis and HCC development but also to identify their translational targets in order to ultimately develop new therapeutic strategies.


Project members

Noteworthy publications
Hepatocyte proteomes reveal the role of protein disulfide isomerase 4 in alpha 1-antitrypsin deficiency.
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 : innovation in hepatology ; 2021 Apr 24
A Particular SORL1 Micro-haplotype May Prevent Severe Liver Disease in a French Cohort of Alpha 1-Antitrypsin-deficient Children.
Joly P, Ruiz M, Garin R, Karatas E, Lachaux A, Restier L, Belmalih A, Renoux C, Lombard C, Dechomet M, Bouchecareilh M
Journal of pediatric gastroenterology and nutrition ; 2021 Sep 01
Liver disease related to alpha1-antitrypsin deficiency in French children: The DEFI-ALPHA cohort.
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 international : official journal of the International Association for the Study of the Liver ; 2019 Jun 01
SERPINA1 and MAN1B1 polymorphisms are not linked to severe liver disease in a French cohort of alpha-1 antitrypsin deficiency children.
Joly P, Lachaux A, Ruiz M, Restier L, Belmalih A, Chapuis-Cellier C, Francina A, Renoux C, Bouchecareilh M
Liver international : official journal of the International Association for the Study of the Liver ; 2017 Nov 01
The histone deacetylase inhibitor, Vorinostat, represses hypoxia inducible factor 1 alpha expression through translational inhibition.
Hutt DM, Roth DM, Vignaud H, Cullin C, Bouchecareilh M
PloS one ; 2014 Aug 28

2-Molecular bases of tumor invasion (V. Moreau / F. SALTEL)

 

Reorganization of the actin cytoskeleton is important for cell migration, cell shape change, and interactions with other cells and the environment. Abnormal cell migration and invasion is a characteristic of malignant cancer cells and is one component of metastasis, the major clinical problem in cancer. Consequently, alterations in cytoskeletal signalling pathways are increasingly being recognized as important for cancer invasion and metastasis. We are mainly working on Invadosomes.

Our group uses a wide range of biochemical, cell biological methods and animal models to study how actin cytoskeleton is regulated and involved in hepatocellular carcinoma cell invasion.

Our work focuses on :

• RhoGTases (RhoE/Rnd3p190RhoGAP)

Actin-binding proteins such as Fascin-1

• Translation machinery, more specifically eIF3 factors

• Discoidin Domain Receptors, DDR1 & DDR2

 

 


Project members

Noteworthy publications
Silencing of RND3/RHOE inhibits the growth of human hepatocellular carcinoma and is associated with reversible senescence.
Basbous S, Paysan L, Sena S, Allain N, Hiriart JB, Dugot-Senant N, Rousseau B, Chevret E, Lagrée V, Moreau V
Cancer gene therapy ; 2022 Mar 07
Discoidin Domain Receptor 2 orchestrates melanoma resistance combining phenotype switching and proliferation.
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, Dugot-Senant N, Rousseau B, Merlio JP, Pham-Ledart A, Vergier B, Tartare-Deckert S, Moreau V, Saltel F
Oncogene ; 2022 Mar 23
Combining laser capture microdissection and proteomics reveals an active translation machinery controlling invadosome formation.
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, Saltel F
Nature communications ; 2018 May 23
Rnd3/RhoE expression is regulated by G-actin through MKL1-SRF signaling pathway.
Piquet L, Robbe T, Neaud V, Basbous S, Rosciglione S, Saltel F, Moreau V
Experimental cell research ; 2018 Sep 15
Cancer-associated mutations in the protrusion-targeting region of p190RhoGAP impact tumor cell migration.
Binamé F, Bidaud-Meynard A, Magnan L, Piquet L, Montibus B, Chabadel A, Saltel F, Lagrée V, Moreau V
The Journal of cell biology ; 2016 Sep 26

3- Cell-cell communications & Tumor microenvironment remodelling (F. SALTEL / V. MOREAU)


Project members

Noteworthy publications
Discoidin Domain Receptor 2 orchestrates melanoma resistance combining phenotype switching and proliferation.
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, Dugot-Senant N, Rousseau B, Merlio JP, Pham-Ledart A, Vergier B, Tartare-Deckert S, Moreau V, Saltel F
Oncogene ; 2022 Mar 23
Multitasking discoidin domain receptors are involved in several and specific hallmarks of cancer.
Henriet E, Sala M, Abou Hammoud A, Tuariihionoa A, Di Martino J, Ros M, Saltel F
Cell adhesion & migration ; 2018 Jan 01
TGF-β1 promotes linear invadosome formation in hepatocellular carcinoma cells, through DDR1 up-regulation and collagen I cross-linking.
Ezzoukhry Z, Henriet E, Piquet L, Boyé K, Bioulac-Sage P, Balabaud C, Couchy G, Zucman-Rossi J, Moreau V, Saltel F
European journal of cell biology ; 2016 Nov 01
Discoidin domain receptor 1 controls linear invadosome formation via a Cdc42-Tuba pathway.
Juin A, Di Martino J, Leitinger B, Henriet E, Gary AS, Paysan L, Bomo J, Baffet G, Gauthier-Rouvière C, Rosenbaum J, Moreau V, Saltel F
The Journal of cell biology ; 2014 Nov 24

4-Proteomic profilling for liver cancer diagnosis, prognosis and theranostics


Project members

Noteworthy publications
Proteomic Profiling of Hepatocellular Adenomas Paves the Way to Diagnostic and Prognostic Approaches.
Dourthe C, Julien C, Di Tommaso S, Dupuy JW, Dugot-Senant N, Brochard A, Le Bail B, Blanc JF, Chiche L, Balabaud C, Bioulac-Sage P, Saltel F, Raymond AA
Hepatology (Baltimore, Md.) ; 2021 Sep 01
ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice.
Sala M, Gonzales D, Leste-Lasserre T, Dugot-Senant N, Paradis V, Di Tommaso S, Dupuy JW, Pitard V, Dourthe C, Sciarra A, Sempoux C, Ferrell LD, Clouston AD, Miller G, Yeh MM, Thung S, Gouw ASH, Quaglia A, Han J, Huan J, Fan C, Crawford J, Nakanuma Y, Harada K, le Bail B, Castain C, Frulio N, Trillaud H, Possenti L, Blanc JF, Chiche L, Laurent C, Balabaud C, Bioulac-Sage P, Raymond AA, Saltel F
Hepatology communications ; 2020 Apr 11
Argininosuccinate synthase 1 (ASS1): A marker of unclassified hepatocellular adenoma and high bleeding risk.
Henriet E, Abou Hammoud A, 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
Hepatology (Baltimore, Md.) ; 2017 Dec 01

Jobs offers


Team’s noteworthy publications

Silencing of RND3/RHOE inhibits the growth of human hepatocellular carcinoma and is associated with reversible senescence.
Basbous S, Paysan L, Sena S, Allain N, Hiriart JB, Dugot-Senant N, Rousseau B, Chevret E, Lagrée V, Moreau V
Cancer gene therapy ; 2022 Mar 07
Discoidin Domain Receptor 2 orchestrates melanoma resistance combining phenotype switching and proliferation.
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, Dugot-Senant N, Rousseau B, Merlio JP, Pham-Ledart A, Vergier B, Tartare-Deckert S, Moreau V, Saltel F
Oncogene ; 2022 Mar 23
Proteomic Profiling of Hepatocellular Adenomas Paves the Way to Diagnostic and Prognostic Approaches.
Dourthe C, Julien C, Di Tommaso S, Dupuy JW, Dugot-Senant N, Brochard A, Le Bail B, Blanc JF, Chiche L, Balabaud C, Bioulac-Sage P, Saltel F, Raymond AA
Hepatology (Baltimore, Md.) ; 2021 Sep 01
Hepatocyte proteomes reveal the role of protein disulfide isomerase 4 in alpha 1-antitrypsin deficiency.
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 : innovation in hepatology ; 2021 Apr 24
Combining laser capture microdissection and proteomics reveals an active translation machinery controlling invadosome formation.
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, Saltel F
Nature communications ; 2018 May 23


Partners

Team leaders

Violaine MOREAU
Research Director / DR

Frédéric SALTEL
Research Director / DR


Team members

Nathalie ALLAIN
Technician / Tech

Charles BALABAUD
Professor Clinician Emeritus / PUPH-EM

Sara BASBOUS
Post PhD Researcher / Post-doc

Clotilde BILLOTTET
Lecturer / MCU

Paulette BIOULAC-SAGE
Professor Clinician Emeritus / PUPH-EM

Jean-Frédéric BLANC
Professor Clinician / PU-PH

Benjamin BONNARD
Post PhD Researcher / Post-doc

Marion BOUCHECAREILH
Researcher / CR

Laurence CHICHE
Professor Clinician / PU-PH

Camille DANTZER
PhD Student / Doc

Victor DE LEDINGHEN
Professor Clinician / PU-PH

Adèle DELAMARRE
PhD Student / Doc

Lydia DIF
PhD Student / Doc

Arnaud JABOUILLE
Researcher / CR

Brigitte LE BAIL
Professor Clinician / PU-PH

Alexandra LEHMANN
PhD Student / Doc

Céline LEON
Engineer / IE

Isabelle MAHOUCHE
Engineer Assistant / AI

Arthur MARICHEZ
Research student / Année recherche

Mélanie MOREAU
PhD Student / Doc

Violaine MOREAU
Research Director / DR

Véronique NEAUD
Technician / Tech

Léa NORMAND
PhD Student / Doc

Mathilde PINAULT
PhD Student / Doc

Anne-Aurélie RAYMOND
Research Engineer / IR

Lucille ROUYER
Engineer / IE

Frédéric SALTEL
Research Director / DR