Our Research

Cancer cell communication with its microenvironment plays a key role in tumor progression and metastatic dissemination. The “Cancer cell signalling” team aims at understanding how deregulation of cell phospho-signaling promotes this neoplastic process and uses this information to develop novel points of therapeutic intervention.

Our research focuses on tyrosine kinase signaling with a specific interest for the Src oncogene in intestinal tumors. In recent years, we discovered key mechanisms in the control of Src tumor activity, which involve its unstructured region and an ubiquitination-dependent mechanism hold by the SLAP tumor suppressive adaptor. By phosphoproteomics, we show that vesicular trafficking regulators and adhesive pseudo-kinases are critical components of this invasive program. Finally, we have identified two novel tyrosine kinase signaling receptors that mediate cancer progression by the tumor microenvironment with potential therapeutic interest.

We continue our research by studying (i) SLAP signaling in intestinal tumors; (ii) Src kinase regulation by its intrinsically disordered region; (iii) oncogenic signaling of PEAK pseudo-kinases; and (iv) the signaling mechanisms of the identified tumor microenvironment receptors and their therapeutic inhibition.

For this, we are combining structural, biochemical, proteomics and cell biological methods with several intestinal cancer models, including nude mice xenografts and genetically modified mouse models, patients derived organoids and others.

NMR team of the University of Barcelona with which we collaborate

L'agence nationale de la recherche | Université de Rennes 1 | Université de Rennes 1                    AnnexeIV_AAP Nérée        Ligue nationale contre le cancer — Wikipédia                 CNRS INNOVATION : Biosolver – une première dans le domaine médical | biosolver   

2022

  • Regulation of Src tumor activity by its N-terminal intrinsically disordered region. Aponte E, Lafitte M, Sirvent A, Simon V, Barbery M, Fourgous E, Boublik Y, Maffei M, Armand F, Hamelin R, Pannequin J, Fort P, Pons M, Roche S. Oncogene. 2022 Jan 9. Epub ahead of print. Pubmed

2021

  • SHED-Dependent Oncogenic Signaling of the PEAK3 Pseudo-Kinase. Ounoughene Y, Fourgous E, Boublik Y, Saland E, Guiraud N, Recher C, Urbach S, Fort P, Sarry JE, Fesquet D, Roche S. Cancers (Basel). 2021 Dec 17;13(24):6344. Pubmed

2020

  • Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis. Audrey Sirvent, Rudy Mevizou, Dana Naim, Marie Lafitte, Serge Roche/ Cancers (Basel);12(8):E2014. Pubmed
  • Collagen Kinase Receptors as Potential Therapeutic Targets in Metastatic Colon Cancer. Lafitte M, Sirvent A, Roche S. Front Oncol. 10:125. Pubmed

2019

  • Roles of exosomes in metastatic colon cancer. Lafitte M, Lecointre C, Roche S. Physiol Cell Physiol. 2019 Jul 10. Pubmed
  • Control of Tyrosine Kinase Signalling by Small Adaptors in Colorectal Cancer. Mevizou R, Sirvent A, Roche S. Cancers (Basel). 11(5). Pubmed
  • SHEDding light on the role of Pragmin pseudo-kinases in cancer. Roche S, Lecointre C, Simon V, Labesse G. Am J Cancer Res. 9(2):449-454. Pubmed

2018

  • DDR1 inhibition as a new therapeutic strategy for colorectal cancer. Sirvent A, Lafitte M, Roche S. Mol Cell Oncol. 5(4):e1465882. Pubmed
  • Dimerization of the Pragmin Pseudo-Kinase Regulates Protein Tyrosine Phosphorylation. Lecointre C, Simon V, Kerneur C, Allemand F, Fournet A, Montarras I, Pons JL, Gelin M, Brignatz C, Urbach S, Labesse G, Roche S.  pii: S0969-2126(18)30040-6. Pubmed
  • Inhibition of DDR1-BCR signalling by nilotinib as a new therapeutic strategy for metastatic colorectal cancer. Jeitany M, Leroy C, Tosti P, Lafitte M, Le Guet J, Simon V, Bonenfant D, Robert B, Grillet F, Mollevi C, El Messaoudi S, Otandault A, Canterel-Thouennon L, Busson M, Thierry AR, Martineau P, Pannequin J, Roche S, Sirvent A. EMBO Mol Med. pii : e7918. Pubmed

2017

  • Syntenin mediates SRC function in exosomal cell-to-cell communication. Imjeti NS, Menck K, Egea-Jimenez AL, Lecointre C, Lembo F, Bouguenina H, Badache A, Ghossoub R, David G, Roche S, Zimmermann P. Proc Natl Acad Sci U S A. pii: 201713433. Pubmed
  • Therapeutic Activity of Anti-AXL Antibody against Triple-Negative Breast Cancer Patient-Derived Xenografts and Metastasis. Leconet W, Chentouf M, du Manoir S, Chevalier C, Sirvent A, Aït-Arsa I, Busson M, Jarlier M, Radosevic-Robin N, Theillet C, Chalbos D, Pasquet JM, Pèlegrin A, Larbouret C, Robert B. Clin Cancer Res. 23(11):2806-2816. Pubmed
  • The Unique Domain Forms a Fuzzy Intramolecular Complex in Src Family Kinases. Arbesú M, Maffei M, Cordeiro TN, Teixeira JM, Pérez Y, Bernadó P, Roche S, Pons M. Structure. 2126:30042-4. Pubmed

2016

  • The role of small adaptor proteins in the control of oncogenic signalingr driven by tyrosine kinases in human cancer. Naudin C, Chevalier C, Roche S. Oncotarget. 7:11033-55. Pubmed
  • TOM1L1 drives membrane delivery of MT1-MMP to promote ERBB2-induced breast cancer cell invasion. Chevalier C, Collin G, Descamps S, Touaitahuata H, Simon V, Reymond N, Fernandez L, Milhiet PE, Georget V, Urbach S, Lasorsa L, Orsetti B, Boissière-Michot F, Lopez-Crapez E, Theillet C, Roche S, Benistant C. Nat Commun. 7:10765. Pubmed
  • Vesicular trafficking regulators are new players in breast cancer progression: Role of TOM1L1 in ERBB2-dependent invasion. Chevalier C, Roche S, Bénistant C. Mol Cell Oncol. 3:e1182241. Pubmed

 

2015

  • Contribution of phosphoproteomics in understanding SRC signaling in normal and tumor cells. Sirvent A, Urbach S, Roche S. 15:232-44. Pubmed
  • Progastrin a new pro-angiogenic factor in colorectal cancer. Najib S, Kowalski-Chauvel A, Do C, Roche S, Cohen-Jonathan-Moyal E, Seva C. Oncogene. 34:3120-30. Pubmed
  • The SH3 Domain Acts as a Scaffold for the N-Terminal Intrinsically Disordered Regions of c-Src. Maffei M, Arbesú M, Le Roux AL, Amata I, Roche S, Pons M. Structure. 23:893-902. Pubmed
  • CBL controls a tyrosine kinase network involving AXL, SYK and LYN in nilotinib-resistant chronic myeloid leukaemia. Gioia R, Trégoat C, Dumas PY, Lagarde V, Prouzet-Mauléon V, Desplat V, Sirvent A, Praloran V, Lippert E, Villacreces A, Leconet W, Robert B, Vigon I, Roche S, Mahon FX, Pasquet JM. J Pathol. 237:14-24. Pubmed
  • YES oncogenic activity is specified by its SH4 domain and regulates RAS/MAPK signaling in colon carcinoma cells. Dubois F, Leroy C, Simon V, Benistant C, Roche S. Am J Cancer Res. 5:1972-87. Pubmed
  • ABL tyrosine kinase inhibition variable effects on the invasive properties of different triple negative breast cancer cell lines. Chevalier C, Cannet A, Descamps S, Sirvent A, Simon V, Roche S, Benistant C. PLoS One. 10:e0118854 Pubmed

2014

  • Analysis of oncogenic signaling induced by tyrosine kinases in tumors by SILAC-based quantitative proteomic approach. Sirvent A, Urbach S, Roche S. Med Sci (Paris). 30:558-66. Pubmed
  • SLAP displays tumour suppressor functions in colorectal cancer via destabilization of the SRC substrate EPHA2. Naudin C, Sirvent A, Leroy C, Larive R, Simon V, Pannequin J, Bourgaux JF, Pierre J, Robert B, Hollande F, Roche S. Nat Commun. 5:3159. Pubmed
  • Suppressor of cytokine signaling 1 modulates invasion and metastatic potential of colorectal cancer cells. David M, Naudin C, Letourneur M, Polrot M, Renoir JM, Lazar V, Dessen P, Roche S, Bertoglio J, Pierre J. Mol Oncol. 8:942-55. Pubmed

2013

  • The short form of RON is expressed in acute myeloid leukemia and sensitizes leukemic cells to cMET inhibitors. Fialin C, Larrue C, Vergez F, Sarry JE, Bertoli S, Mansat-De Mas V, Demur C, Delabesse E, Payrastre B, Manenti S, Roche S, Récher C.  27(2):325-35. Pubmed

2012

  • Analysis of SRC oncogenic signaling in colorectal cancer by stable isotope labeling with heavy amino acids in mouse xenografts. Sirvent A, Vigy O, Orsetti B, Urbach S, Roche S. Mol Cell Proteomics. 11(12):1937-50. Pubmed
  • Oncogenic signaling by tyrosine kinases of the SRC family in advanced colorectal cancer. Sirvent A, Benistant C, Roche S. Am J Cancer Res. 2(4):357-71. Pubmed

2011

  • Quantitative phosphoproteomics revealed interplay between Syk and Lyn in the resistance to nilotinib in chronic myeloid leukemia cells. Gioia R, Leroy C, Drullion C, Lagarde V, Etienne G, Dulucq S, Lippert E, Roche S, Mahon FX, Pasquet JM. Blood. 118(8):2211-21. Pubmed
  • Specific oncogenic activity of the Src-family tyrosine kinase c-Yes in colon carcinoma cells. Sancier F, Dumont A, Sirvent A, Paquay de Plater L, Edmonds T, David G, Jan M, de Montrion C, Cogé F, Léonce S, Burbridge M, Bruno A, Boutin JA, Lockhart B, Roche S, Cruzalegui F. PLoS One. 6(2):e17237. Pubmed

 

2010

  • Src family tyrosine kinases-driven colon cancer cell invasion is induced by Csk membrane delocalization. Sirvent A, Bénistant C, Pannequin J, Veracini L, Simon V, Bourgaux JF, Hollande F, Cruzalegui F, Roche S. Oncogene. 29(9):1303-15. Pubmed
  • A non-catalytic function of the Src family tyrosine kinases controls prolactin-induced Jak2 signaling. García-Martínez JM, Calcabrini A, González L, Martín-Forero E, Agulló-Ortuño MT, Simon V, Watkin H, Anderson SM, Roche S, Martín-Pérez J. Cell Signal. 22(3):415-26. Pubmed

2009

  • Alternative splicing modulates autoinhibition and SH3 accessibility in the Src kinase Fyn. Brignatz C, Paronetto MP, Opi S, Cappellari M, Audebert S, Feuillet V, Bismuth G, Roche S, Arold ST, Sette C, Collette Y. Mol Cell Biol. 29(24):6438-48. Pubmed
  • Quantitative phosphoproteomics reveals a cluster of tyrosine kinases that mediates SRC invasive activity in advanced colon carcinoma cells. Leroy C, Fialin C, Sirvent A, Simon V, Urbach S, Poncet J, Robert B, Jouin P, Roche S. Cancer Res. 69(6):2279-86. Pubmed

2008

  • Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression. Mahon FX, Hayette S, Lagarde V, Belloc F, Turcq B, Nicolini F, Belanger C, Manley PW, Leroy C, Etienne G, Roche S, Pasquet JM. Cancer Res. 68(23):9809-16 Pubmed
  • Cytoplasmic signalling by the c-Abl tyrosine kinase in normal and cancer cells. Sirvent A, Benistant C, Roche S. Biol Cell. 100(11):617-31. Pubmed
  • The Src-like adaptor protein regulates PDGF-induced actin dorsal ruffles in a c-Cbl-dependent manner. Sirvent A, Leroy C, Boureux A, Simon V, Roche S. Oncogene. 27(24):3494-500. Pubmed
  • The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1. Veracini L, Simon V, Richard V, Schraven B, Horejsi V, Roche S, Benistant C. J Cell Biol. 182(3):603-14. Pubmed

Cancer cell signaling

Serge ROCHE

Group Leader (Research Director DR1)

Team Members

  • Yvan BOUBLIK
    (IR-Recherche) +33 (0)4 34 35 97 17
  • Florent CAUCHOIX
    (Stagiaire) +33 (0)4 34 35 95 03
  • Audrey COQUARD-SIRVENT
    (Chercheur) +33 (0)4 34 35 95 03
  • Kevin ESPIE
    (IE-Recherche) +33 (0)4 34 35 95 03
  • Elise FOURGOUS
    (IE-Recherche) +33 (0)4 34 35 95 03
  • Dana NAIM
    (Doctorant) +33 (0)4 34 35 95 70
  • Julie NGUYEN
    (Post-Doc) +33 (0)4 34 35 95 03
  • Serge ROCHE Chef d'équipe
    (Chercheur DR1) +33 (0)4 34 35 95 03
  • Contact us

    Replace the name and address below with that of the member to contact
    firstname.name@crbm.cnrs.fr

    Le programme Equipes Labéllisées | Ligue contre le Cancer

    OUR PUBLICATIONS

    Dimerization of the Pragmin Pseudo-Kinase Regulates Protein Tyrosine Phosphorylation.

    Lecointre C, Simon V, Kerneur C, Allemand F, Fournet A, Montarras I, Pons JL, Gelin M, Brignatz C, Urbach S, Labesse G, Roche S.

    Structure. 2018 Apr 3;26(4):545-554.e4.

    Pubmed

    Inhibition of DDR1-BCR signalling by nilotinib as a new therapeutic strategy for metastatic colorectal cancer.

    Jeitany M, Leroy C, Tosti P, Lafitte M, Le Guet J, Simon V, Bonenfant D, Robert B, Grillet F, Mollevi C, El Messaoudi S, Otandault A, Canterel-Thouennon L, Busson M, Thierry AR, Martineau P, Pannequin J, Roche* S, Sirvent* A.

    EMBO Mol Med. 2018 Apr;10(4):e7918.

    Pubmed

    TOM1L1 drives membrane delivery of MT1-MMP to promote ERBB2-induced breast cancer cell invasion.

    Chevalier C, Collin G, Descamps S, Touaitahuata H, Simon V, Reymond N, Fernandez L, Milhiet PE, Georget V, Urbach S, Lasorsa L, Orsetti B, Boissière-Michot F, Lopez-Crapez E, Theillet C, Roche* S, Benistant* C.

    Nat Commun. 2016 Feb 22;7:10765.

    Pubmed