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


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