Equipe 11

Team 11 : Sophie Tartare-Deckert
MICROENVIRONMENT, SIGNALLING AND CANCER
Previous activities
The tumor microenvironment regulates cancer progression through complex and dynamic interactions between tumor cells, activated stromal cells and components of the extracellular matrix, creating a co-evolving ecosystem. Stromal cells usually include tumor-associated fibroblasts, endothelial cells, and infiltrating inflammatory and immune cells. The communication between cancer cells and its stroma in a tumor not only alter the biological properties of the cancer cell, but also of the different cells in the stroma, promoting tumor growth, metastasis and resistance to therapeutics. Understanding how the tumor ecosystem fosters malignant growth, invasion and metastasis cascade should open up new avenues for stroma-targeted therapies for cancer. Our laboratory is interested in the crosstalk between cancer cells and their stroma within the lymph node microenvironment in two tumor models, melanoma, an aggressive clinical form of skin cancers and lymphoma. The lymph node is the first locus of expansion for invasive melanoma cells and one of the natural niches of malignant B-cells. In a first axis, we are following up our work on the molecular and cellular mechanisms governing melanoma development with a particular focus on SPARC, a matricellular protein that modulates the dialogue between tumor cells and their stroma. Our lab achieved important discoveries such as: (i) the role of SPARC as a matricellular regulator of Epithelial Mesenchymal Transition (EMT) and p53-dependent cell survival; and (ii) the epigenetic silencing of the tyrosine kinase Syk and its contribution in melanoma senescence bypass, Kit signaling and metastasis. Ongoing projects in the lab are pursuing our initial results on SPARC and Syk using different mouse melanoma models and the study of the role of tumor-associated fibroblasts within the lymphatic metastatic niche in survival and therapeutic resistance. Our aim is to translate our results on melanoma to the clinic. The second axis is devoted to the understanding of the molecular and cellular mechanisms involved in the environment-mediated cell death resistance observed in multiple lymphoid malignancies. Our past studies on the signaling pathways downstream Syk family kinases in normal and pathological leukocytes led to : (i) the characterization of several Syk effectors, including the Rho GTPases activators VAV and the adapter 3BP2; (ii) the identification in chronic lymphocytic leukemia of a Syk-PI3K-Akt axis involved in chemokine-induced and FOXO3-dependant cell survival and in the proteasome-mediated regulation of the antiapoptotic protein Mcl-1. Current projects aim at deciphering how extracellular proteins such as SPARC and stromal cells impact on lymphoid malignancies resistance to cell death and treatment. Our work would have strong relevance with respect to the dynamic and reciprocal interactions between cancer cells and their microenvironment and would bring a better understanding of melanoma and lymphoma malignancies and of the biology of the lymphatic system in cancer and metastasis. Beyond their cognitive aspect on signaling pathways that control the pathological cell-cell and cell-matrix communication within the tumor microenvironment, our findings would have important implications for identification of novel biomarkers for invaded lymph nodes and potential targets, and improvements of the clinical management of the diseases.
Major Publications
2015 Tichet M, Prod'Homme V, Fenouille N, Ambrosetti D, Mallavialle A, Cerezo M, Ohanna M, Audebert S, Rocchi S, Giacchero D, Boukari F, Allegra M, Chambard JC, Lacour JP, Michiels JF, Borg JP, Deckert M, Tartare-Deckert S. Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis. Nat Commun. 2015 Apr 30;6 Prod'Homme V, Boyer L, Dubois N, Mallavialle A, Munro P, Mouska X, Coste I, Rottapel R, Tartare-Deckert S, Deckert M. Cherubism allele heterozygosity amplifies microbe-induced inflammatory responses in murine macrophages. J Clin Invest. 2015 Apr 1;125(4):1396-400 2013 Larbret F, Dubois N, Brau F, Guillemot E, Mahiddine K, Tartare-Deckert S, Verhasselt V, Deckert, M. Technical Advance: Actin CytoFRET, a novel FRET flow cytometry method for detection of actin dynamics in resting and activated T cell. J Leukoc Biol. 2013 Jun 26. 2012 Deckert, M. and Tartare-Deckert, S. Senescence escape in melanoma: role of spleen tyrosine kinase Syk. In Tumor dormancy and cellular quiescence. Editor M. A. Hayat. Springer Science. (in press). Fenouille, N., Tichet, M., Dufies, M., Pottier, A., Mogha, A., Soo, J. K., Rocchi, S., Malavialle, A., Khammari, A., Lacour, J-P., Galibert, MD., Ballotti, R., Deckert, M. and Tartare-Deckert, S. The epithelial-mesenchymal transition (EMT) regulatory factor Slug (SNAI2) is a downstream target of SPARC and AKT in promoting melanoma cell invasion. PLoS One. 2012. 7(7):e40378. Epub 2012 Jul 20. Puissant, A., Dufies, M, Fenouille, N, Ben Sahra, I., Jacquel, A., Robert, G., Cluzeau, T., Deckert, M., Tichet, M., Cheli, Y., Cassuto, J. P., Raynaud, S., Legros, L., Pasquet, J. M., Mahon, F. X., Luciano, F and Auberger, P. Imatinib triggers mesenchymal-like conversion of CML cells associated with increased aggressiveness. J Mol Cell Biol, 2012. Aug;4(4):207-20. Epub 2012 Mar 31. Cheli Y, Giuliano S, Fenouille N, Allegra M, Hofman V, Hofman P, Bahadoran P, Lacour JP, Tartare-Deckert S, Bertolotto C, Ballotti R. 2012. Hypoxia and MITF control metastatic behaviour in mouse and human melanoma cells. Oncogene, 2012 May 10;31(19):2461-70. doi: 10.1038/onc.2011.425. Epub 2011 Sep 26 2011 Fenouille, N., Puissant, A., Tichet, M., Zimniak, G., Abbe, P., Mallavialle, A., Rocchi, S., Ortonne, J.-P., Deckert, M., Ballotti, R., and Tartare-Deckert, S. 2011. SPARC functions as an anti-stress factor by inactivating p53 through Akt-mediated MDM2 phosphorylation to promote melanoma cell survival. Oncogene, Dec 8;30(49):4887-900. Colacios C., Casemayou A., Dejean A.S., Gaits Iacovoni F., Pedros C., Bernard I., Lagrange D., Deckert M., Lamouroux L., Jagodic M., Olsson T., Liblau R.S., Gilbert J. Fournié, G.J., and Saoudi A. 2011. The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cells development. J Exp Med, Oct 24;208(11):2183-91. Levaot N., Dimitriou, I. Sircoulomb, F., Voytyuk, O, Chandrakumar, A., Deckert, M., Krzyzanowski, P.M., Scotter, A., Gu, S., Janmohamed, S., Cong, F., Simoncic, P.D., Ueki, Y., La Rose, J., and Rottapel. R. 2011. Loss of Tankyrase-mediated destruction of 3BP2 is the underlying pathogenic mechanism of cherubism. Cell, Dec 9;147(6):1324-39. Tomic, T., Botton, T., Cerezo, M., Robert, G., Luciano, F., Puissant, A., Gounon, P., Allegra, M., Bertolotto, C., Bereder, J-M, Tartare-Deckert, S., Bahadoran, P., Auberger, P., Ballotti, R., and Rocchi, S. 2011. Metformin inhibits melanoma development through autophagy and apoptosis mechanisms. Cell Death Dis, Sep 1;2:e199. doi: 10.1038/cddis.2011.86. [Epub ahead of print]. Essafi, M., Baudot, A., Mouska, X., Cassuto, J., Ticchioni, M., and Deckert, M. 2011. Cell permeant TAT-FOXO3a fusion proteins induce leukemic cell death. Mol. Cancer Ther. Jan;10(1):37-46. Fenouille, N., Robert, G., Tichet, M., Puissant, A., Dufies, M., Rocchi, S., Ortonne, J.-P., Deckert, M., Ballotti, R., and Tartare-Deckert, S. 2011. The p53/p21(Cip1/Waf1) pathway mediates the effects of SPARC on melanoma cell cycle progression. Pigment Cell Melanoma Res. Feb;24(1):219-32. Botton, T., Puissant, A., Cheli, Y., Tomic, T., Giuliano, S., Fajas, L., Deckert, M., Ortonne, J.P., Bertolotto, C., Tartare-Deckert, S., Ballotti, R., and Rocchi, S. 2011. Ciglitazone negatively regulates CXCL1 signaling through MITF to suppress melanoma growth. Cell Death Differ, Jan;18(1):109-21. 2010 Fenouille N, Puissant A, Dufies M, Robert G, Jacquel A, Ohanna M, Deckert M, Pasquet JM, Mahon FX, Cassuto JP, Raynaud S, Auberger, P. and Tartare-Deckert, S. 2010. Permanent activation of the Fyn/Erk axis mediates Imatinib resistance in Chronic Myelogenous Leukemia cells through increased expression of intracellular SPARC. Cancer Res. 2010 Dec 1;70(23):9659-70. Equal contribution. Puissant, A., Robert, G., Fenouille, N., Luciano, F., Cassuto, J.P., Raynaud, S., and Auberger, P. 2010. Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation. Cancer Res. 70, 1042-52. 2009 Bailet, O., Fenouille, N., Abbe, P., Robert, G., Rocchi, S., Gonthier, N., Denoyelle, C., Ticchioni, M., Ortonne, J.P., Ballotti, R., Deckert, M., and. Tartare-Deckert, S. 2009. Spleen tyrosine kinase functions as a tumor suppressor in melanoma cells by inducing senescence-like growth arrest. Cancer Res. 69, 2748-56. Baudot, A.D., Jeandel, P.Y., Mouska, X., Maurer, U., Tartare-Deckert, S., Raynaud, S.D., Cassuto, J.P., Ticchioni, M., and Deckert, M. 2009. The tyrosine kinase Syk regulates the survival of chronic lymphocytic leukemia B cells through PKCdelta and proteasome-dependent regulation of Mcl-1 expression. Oncogene. 28, 3261-73. Botton, T., Puissant, A., Bahadoran, P., Annicotte, J.S., Fajas, L., Ortonne, J.P., Gozzerino, G., Zamoum, T., Tartare-Deckert, S., Bertolotto, C., Ballotti, R., and Rocchi, S. 2009. In vitro and in vivo anti-melanoma effects of ciglitazone. J Invest Dermatol. 129, 1208-18. Essafi-Benkhadir, K., Grosso, S., Puissant, A., Robert, G., Essafi, M., Deckert, M., Chamorey, E., Dassonville, O., Milano, G., Auberger, P., and Pages, G. 2009. Dual role of Sp3 transcription factor as an inducer of apoptosis and a marker of tumour aggressiveness. PLoS One. 4, e4478. Grosso, S., Puissant, A., Dufies, M., Colosetti, P., Jacquel, A., Lebrigand, K., Barbry, P., Deckert, M., Cassuto, J.P., Mari, B., and Auberger, P. 2009. Gene expression profiling of imatinib and PD166326-resistant CML cell lines identifies Fyn as a gene associated with resistance to BCR-ABL inhibitors. Mol Cancer Ther. 8, 1924-33. Marchetti, S., Gamas, P., Belhacene, N., Grosso, S., Pradelli, L.A., Colosetti, P., Johansen, C., Iversen, L., Deckert, M., Luciano, F., Hofman, P., Ortonne, N., Khemis, A., Mari, B., Ortonne, J.P., Ricci, J.E., and Auberger, P. 2009. The caspase-cleaved form of LYN mediates a psoriasis-like inflammatory syndrome in mice. Embo J*. 28, 2449-60.

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