S. Pyronnet / C. Bousquet

  Protein Synthesis and secretion in oncogenesis

 

 

 

 

 

 

 

Our research project at a glance

 

Cancer cells must double their protein content before dividing (proliferation), and both cancer and surrounding cells (especially cancer-activated fibroblasts) synthetize and secrete proteins critical for tumor growth, metastasis spreading and resistance to treatment. Our group searches how protein synthesis and related signaling pathways are regulated in healthy cells, how they become altered in malignant tumors and whether they can be targeted for therapeutic intervention.

 

Objectives

 

Through biochemical, cellular and in vivo models our fundamental objective is to understand how mRNA translation into protein is regulated. The function of both global (through canonical translation initiation complexes) and mRNA-specific translational factors and their respective regulations by selective signaling pathways are explored. These new mechanistic insights are then very helpful in searching whether and how alterations in the control of protein synthesis play a role in oncogenesis and in resistance to treatment.

Thanks to collaborations with clinicians and local and international industrial partners, the uncovered mechanisms are validated in patient samples and known or new pharmaceutical compounds are tested for their therapeutic potential.

We have a solid background in pancreatic tumors (and accumulating evidence in acute myeloid leukemia) showing that selective translational regulators and/or signaling pathways appears as attractive therapeutic targets. Their targeting can affect tumor growth, metastatic spreading or response to conventional treatments through either direct effects on cancer cells or indirect effects on tumor microenvironment.

 

Key words

 

  • Protein synthesis
  • mRNA translation
  • Signaling pathways
  • Tumor microenvironment
  • Somatostatin
  • Pancreatic cancer
  • Acute myeloid leukemia

 

Selected publications


2019

Müller, D; Shin, S; Goullet de Rugy, T; Samain, R; Baer, R; Strehaiano, M; Masvidal-Sanz, L; Guillermet-Guibert, J; Jean, C; Tsukumo, Y; Sonenberg, N; Marion, F; Guilbaud, N; Hoffmann, JS. ; Larsson, O; Bousquet, C; Pyronnet, S; Martineau, Y

eIF4A inhibition circumvents uncontrolled DNA replication mediated by 4E-BP1 loss in pancreatic cancer Journal Article

JCI Insight, 4 (21), pp. 121951, 2019.

Abstract | Links | BibTeX

Saponaro, C; Thévenet, J; Gmyr, V; Moerman, E; Delalleau, N; Pasquetti, G; Quenon, A; Daoudi, M; Hubert, T; Vantyghem, MC. ; Bousquet, C; Martineau, Y; Kerr-Conte, J; Staels, B; Pattou, F; Bonner, C

The GLP1R Agonist Liraglutide Reduces Hyperglucagonemia Induced by the SGLT2 Inhibitor Dapagliflozin via Somatostatin Release. Journal Article

Cell Rep, 28 (6), pp. 1447-1454, 2019.

Abstract | Links | BibTeX

Neuzillet, C; Tijeras-Raballand, A; Ragulan, C; Cros, J; Patil, Y; Martinet, M; Erkan, M; Kleeff, J; Wilson, J; Apte, M; Tosolini, M; Wilson, AS. ; Delvecchio, FR. ; Bousquet, C; Paradis, V; Hammel, P; Sadanandam, A; Kocher, HM.

Inter- and intra-tumoral heterogeneity in cancer-associated fibroblasts of human pancreatic ductal adenocarcinoma. Journal Article

J Pathol, 248 (1), pp. 51-65, 2019.

Abstract | Links | BibTeX

Goehrig, D; Samain, R; Nigri, J; Wu, Z; Cappello, P; Gabiane, G; Zhang, X; Zhao, Y; Kim, IS. ; Chanal, M; Curto, R; Hervieu, V; de La Fouchardière, C; Novelli, F; Milani, P; Tomasini, R; Bousquet, C; Bertolino, P; Hennino, A

Stromal protein βig-h3 reprogrammes tumour microenvironment in pancreatic cancer. Journal Article

Gut, 68 (4), pp. 693-707, 2019.

Abstract | Links | BibTeX

2018

Günther, T; Tulipano, G; Dournaud, P; Bousquet, C; Csaba, Z; Kreienkamp, HJ. ; Lupp, A; Korbonits, M; Castaño, JP. ; Wester, HJ. ; Culler, M; Melmed, S; Schulz, S

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature. Journal Article

Pharmacoil Rev, 70 (4), pp. 763-835, 2018.

Abstract | Links | BibTeX

Ogier, C; Colombo, PE. ; Bousquet, C; Canterel-Thouennon, L; Sicard, P; Garambois, V; Thomas, G; Gaborit, N; Jarlier, M; Pirot, N; Pugnière, M; Vie, N; Gongora, C; Martineau, P; Robert, B; Pèlegrin, A; Chardès, T; Larbouret, C

Targeting the NRG1/HER3 pathway in tumor cells and cancer-associated fibroblasts with an anti-neuregulin 1 antibody inhibits tumor growth in pre-clinical models of pancreatic cancer. Journal Article

Cancer lett, 432 , pp. 227-236, 2018.

Abstract | Links | BibTeX

2017

Elia, A; Henry-Grant, R; Adiseshiah, C; Marboeuf, C; Buckley, RJ. ; Clemens, MJ. ; Mudan, S; Pyronnet, S

Implication of 4E-BP1 protein dephosphorylation and accumulation in pancreatic cancer cell death induced by combined gemcitabine and TRAIL Journal Article

Cell Death and Dis, (8), pp. 3204, 2017.

Abstract | Links | BibTeX

2016

Moatassim-Billah, S; Duluc, C; Samain, R; Jean, C; Perraud, A; Decaup, E; Cassant-Sourdy, S; Bakri, Y; Selves, J; Schmid, H; Martineau, Y; Mathonnet, M; Pyronnet, S; Bousquet, C

Anti-metastatic potential of somatostatin analog SOM230: Indirect pharmacological targeting of pancreatic cancer-associated fibroblasts Journal Article

Oncotarget, 7 (27), pp. 41584-41598, 2016, ISSN: 1949-2553 (Electronic) 1949-2553 (Linking).

Links | BibTeX

2015

Chalabi-Dchar, M; Cassant-Sourdy, S; Duluc, C; Fanjul, M; Lulka, H; Samain, R; Roche, C; Breibach, F; Delisle, M B; Poupot, M; Dufresne, M; Shimaoka, T; Yonehara, S; Mathonnet, M; Pyronnet, S; Bousquet, C

Loss of Somatostatin Receptor Subtype 2 Promotes Growth of KRAS-Induced Pancreatic Tumors in Mice by Activating PI3K Signaling and Overexpression of CXCL16 Journal Article

Gastroenterology, 148 (7), pp. 1452-65, 2015, ISSN: 1528-0012 (Electronic) 0016-5085 (Linking).

Links | BibTeX

Duluc, C; Moatassim-Billah, S; Chalabi-Dchar, M; Perraud, A; Samain, R; Breibach, F; Gayral, M; Cordelier, P; Delisle, M B; Bousquet-Dubouch, M P; Tomasini, R; Schmid, H; Mathonnet, M; Pyronnet, S; Martineau, Y; Bousquet, C

Pharmacological targeting of the protein synthesis mTOR/4E-BP1 pathway in cancer-associated fibroblasts abrogates pancreatic tumour chemoresistance Journal Article

EMBO Mol Med, 7 (6), pp. 735-53, 2015, ISSN: 1757-4684 (Electronic) 1757-4676 (Linking).

Links | BibTeX

2014

Laval, S; Laklai, H; Fanjul, M; Pucelle, M; Laurell, H; Billon-Gales, A; Le Guellec, S; Delisle, M B; Sonnenberg, A; Susini, C; Pyronnet, S; Bousquet, C

Dual roles of hemidesmosomal proteins in the pancreatic epithelium: the phosphoinositide 3-kinase decides Journal Article

Oncogene, 33 (15), pp. 1934-44, 2014, ISSN: 1476-5594 (Electronic) 0950-9232 (Linking).

Links | BibTeX

Martineau, Y; Azar, R; Muller, D; Lasfargues, C; El Khawand, S; Anesia, R; Pelletier, J; Bousquet, C; Pyronnet, S

Pancreatic tumours escape from translational control through 4E-BP1 loss Journal Article

Oncogene, 33 (11), pp. 1367-74, 2014, ISSN: 1476-5594 (Electronic) 0950-9232 (Linking).

Links | BibTeX

2013

Martineau, Y; Azar, R; Bousquet, C; Pyronnet, S

Anti-oncogenic potential of the eIF4E-binding proteins Journal Article

Oncogene, 32 (6), pp. 671-7, 2013, ISSN: 1476-5594 (Electronic) 0950-9232 (Linking).

Links | BibTeX

2012

Najib, S; Saint-Laurent, N; Esteve, J P; Schulz, S; Boutet-Robinet, E; Fourmy, D; Lattig, J; Mollereau, C; Pyronnet, S; Susini, C; Bousquet, C

A switch of G protein-coupled receptor binding preference from phosphoinositide 3-kinase (PI3K)-p85 to filamin A negatively controls the PI3K pathway Journal Article

Mol Cell Biol, 32 (5), pp. 1004-16, 2012, ISSN: 1098-5549 (Electronic) 0270-7306 (Linking).

Links | BibTeX

2010

Alard, A; Fabre, B; Anesia, R; Marboeuf, C; Pierre, P; Susini, C; Bousquet, C; Pyronnet, S

NAD(P)H quinone-oxydoreductase 1 protects eukaryotic translation initiation factor 4GI from degradation by the proteasome Journal Article

Mol Cell Biol, 30 (4), pp. 1097-105, 2010, ISSN: 1098-5549 (Electronic) 0270-7306 (Linking).

Links | BibTeX

2009

Azar, R; Alard, A; Susini, C; Bousquet, C; Pyronnet, S

4E-BP1 is a target of Smad4 essential for TGFbeta-mediated inhibition of cell proliferation Journal Article

EMBO J, 28 (22), pp. 3514-22, 2009, ISSN: 1460-2075 (Electronic) 0261-4189 (Linking).

Links | BibTeX

Laklai, H; Laval, S; Dumartin, L; Rochaix, P; Hagedorn, M; Bikfalvi, A; Le Guellec, S; Delisle, M B; Schally, A V; Susini, C; Pyronnet, S; Bousquet, C

Thrombospondin-1 is a critical effector of oncosuppressive activity of sst2 somatostatin receptor on pancreatic cancer Journal Article

Proc Natl Acad Sci U S A, 106 (42), pp. 17769-74, 2009, ISSN: 1091-6490 (Electronic) 0027-8424 (Linking).

Links | BibTeX