Group F. Saltel

The overall project is to identify, at cellular and tissue levels, molecular pathways involved in tumor progression.

Research

Metastases development at a distance from a primary site of cancer represents the principal cause of cancer-related mortality. Presently, there is no efficient way to block tumor cell invasion. Significantly, cell invasion relates only to a small part of the tumor and is linked to invasive structures named invadosomes consisting of invasive protrusions that orchestrate tumor cell invasion. Recently, in my group we developed a new methodology to define the proteome of low biological material obtained from subcellular compartment and adapted it to human tissues (hepatocellular carcinoma).

Our work focuses on the link between the matrix tumor microenvironment and cancer cell invasion

Two principal research axes:

• DDR 1 and 2 involvement in tumor progression and invasion
• Translational research on liver tumors using proteomic approach

We highlighted :
• a new organization of invadosomes induced by the type I collagen into its fibrillar organization
• the concept of invadosomes plasticity

Discoidin receptor 1 controls linear invadosome formation and activity.

Video: Tumor cell (blue) seeded on type I collagen fibrils (red) forming linear invadosomes labelled by Tks5 (green)

People

Main publications

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.
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).
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, Nat Cell Biol. 2020 Nov;22(11):1371-1381. doi: 10.1038/s41556-020-00590-w.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, Hepatol Commun 2020, 4, 809–824.
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. Hepatol Comm, 2018 Dec 28;3(2):213-219.
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. Combining laser capture microdissection and proteomics reveals an active translation machinery controlling invadosome formation. Nat Commun. 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;12(4):363-377
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;12(4):324-334.
Nguyen AT, Chia J, Ros M, Hui KM, Saltel F, Bard F. Organelle Specific O-Glycosylation Drives MMP14 Activation, Tumor Growth, and Metastasis.Cancer Cell. 2017 Nov 13;32(5):639-653.e6.
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 Dec;66(6):2016-2028.
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 May 15;130(10):1796-1808.
Ezzoukhry Z*, Henriet E*, Piquet L, Boyé K, Bioulac-Sage P, Balabaud C, Zucman-Rossi J, Moreau V, Saltel F. TGF-b 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.
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)
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. Discoidin domain receptor 1 controls linear invadosome formation via a Cdc42/Tuba pathway.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).
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.
Juin A, Billottet C*, Moreau V*, Destaing O, Albiges-Rizo C, Rosenbaum J, Genot 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.