Parent Category: Laboratoires Published: Friday, 17 February 2012

Oncogenesis and Immunotherapy

 

PIECHACZYK

 Marc PIECHACZYK

 

IGMM - UMR 5535

1919, route de Mende, 34293 Montpellier

 

Phone: +33 4 34 35 96 49

Email:  marc.piechaczyk@igmm.cnrs.fr

 

Website

 

 

Transcription factors constitute essential molecular platforms for the integration of intra- and extracellular signals and their activity is regulated by numerous of post-translational modifications. Yet, the molecular mechanisms whereby their deregulation alters gene expression at the chromatin level to permit adaptation of cancer cells to their environment and to strengthen their agressiveness are still ill-defined. 

In this context, we follow two lines of research. On the one hand, we are addressing why and how the ubiquitous transcription complex AP-1 contributes to the metastatic phenotype and agressiveness of the triple negative breast tumors where it is overactive due to perverted cell signaling and to which extend this knowledge can be used to improve treatments. This issue is particularly important, as metastatic breast cancer is currently the main cause of death by cancer amongst women. On the other hand, we are addressing how protein post-translational modification by SUMOylation can be exploited for better treatment of Acute Myeloid Leukemia (AML) via alteration of gene expression programs. This question is of utmost importance as AMLs are hematomalignancies with dismal outcome whose treatment has not significantly changed for the past 40 years. Our most recent discoveries indicate that alteration of cell SUMOylation opens novel diagnostic and therapeutical perspectives for future treatment of AMLs.

Our project relies on high throughput "omics" approaches, exploitation of cancer databases, the use of patient samples and functional studies conducted in vitro (cellular models) and in vivo (mouse pre-clinical models).

 

Keywords: Acute Myeloid Leukemia, Breast Cancer, Transcriptional Regulation, Ubiquitin-likes

 

 

Main publications

  • Baik, H., Hossein, S-M., Kowalczyk, J., Boulanger, M., Zaghdoudi, S., Salem, T., Sarry, J-E., Hicheri, Y., Cartron, G., Piechaczyk, M. (*) and Bossis, G. Inhibition of the SUMO pathway potentiates all-trans-retinoic acid differentiation of non-promyelocytic acute myeloid leukemia (in revision).
  • Bonet C., Luciani F., Ottavi JF., Leclerc J., Jouenne FM., Boncompagni M., Bille K., Hofman V., Bossis G., Marco de Donatis G., Strub T., Cheli Y., Ohanna M., Luciano F., Marchetti S., Rocchi S., Birling MC., Avril MF., Poulalhon N., Luc T., Bertolotto C.. Deciphering the Role of Oncogenic MITFE318K in Senescence Delay and Melanoma Progression. J Natl Cancer Inst. 109(8). doi: 10.1093/jnci/djw340 (2017).
  • Ul Haq Khan A, Allende-Vega N, Gitenay D, Gerbal-Chaloin S, Gondeau C, Vo DN, Belkahla S, Orecchioni S, Talarico G, Bertolini F , Stanojevic MB, Valdivielso JM, Bejjani F, Jariel-Encontre I, Lopez-Mejia I, Fajas L, Lecellier CH, Hernandez J, Daujat M, and Villalba M. The PDK1 Inhibitor Dichloroacetate Controls Cholesterol Homeostasis Through the ERK5/MEF2 Pathway. Scientific reports (in press).
  • Rawat, V., Goux, W., Piechaczyk, M. and D'Mello, S. R.. c-Fos Protects Neurons Through a Noncanonical Mechanism Involving HDAC3 Interaction: Identification of a 21-Amino Acid Fragment with Neuroprotective Activity. Mol Neurobiol. 53 : 1165-80 (2016).
  • Pelegrin, M., Naranjo-Gomez, M. and Piechaczyk, M. Antiviral Monoclonal Antibodies: Can They Be More Than Simple Neutralizing Agents? Trends Microbiol. 23 : 653-665 (2015).
  • Bossis G;, Sarry JE., Kifagi C., Ristic M., Saland E., Vergez F., Salem T., Boutzen H., Baik H., Brockly F., Pelegrin M., Kaoma T., Vallar L., Récher C., Manenti S., Piechaczyk M. The ROS/SUMO Axis Contributes to the Response of Acute Myeloid Leukemia Cells to Chemotherapeutic Drugs. Cell Reports. 7:1815-23. doi: 10.1016/j.celrep.2014.05.016 (2014).
  • Tempé, D., Vives, E., Brockly, F., Brooks, H., De Rossi, S., Piechaczyk, M. and Bossis, G. SUMOylation of the inducible (c-Fos:c-Jun)/AP-1 transcription complex occurs on target promoters to limit transcriptional activation. Oncogene 33:921-7 (2014).
  • Moquet-Torcy G., Tolza, C., Piechaczyk, M. and Jariel-Encontre, I. Transcriptional complexity and roles of Fra-1/AP-1 at the uPA/Plau locus in aggressive breast cancers. Nucl. Acids Res. 42:11011-24 doi:10.1093/nar/gku814 (2014).
  • Malnou, C. E., Salem, T., Brockly, F., Wodrich, H., Piechaczyk, M. and Jariel-Encontre, I. (2007). Heterodimerization with Jun family members regulates c-Fos nucleocytoplasmic traffic J Biol Chem . 282 : 31046-59
  • Salem T, Gomard T, Court F, Moquet-Torcy G, Brockly F, Forné T, Piechaczyk M. Chromatin loop organization of the junb locus in mouse dendritic cells. Nucleic Acids Res. 41:8908-25. doi: 10.1093/nar/gkt669 (2013).
  • Nasser R, Pelegrin M, Plays M, Gros L, Piechaczyk M. Control of regulatory T cells is necessary for vaccine-like effects of antiviral immunotherapy by monoclonal antibodies. Blood. 2013 Feb 14;121(7):1102-11. doi: 10.1182/blood-2012-06-432153 (2013).
  • Pérez-Benavente B, Garcia JL, Rodríguez MS, Pineda-Lucena A, Piechaczyk M, Font de Mora J, Farràs R. GSK3-SCF(FBXW7) targets JunB for degradation in G2 to preserve chromatid cohesion before anaphase. Oncogene 32:2189-99. doi: 10.1038/onc.2012.235 (2013).
  • Belguise K, Milord S, Galtier F, Moquet-Torcy G, Piechaczyk M, Chalbos D. The PKCθ pathway participates in the aberrant accumulation of Fra-1 protein in invasive ER-negative breast cancer cells. Oncogene 31:4889-97. doi: 10.1038/onc.2011.659 (2012).
  • Sayan AE, Stanford R, Vickery R, Grigorenko E, Diesch J, Kulbicki K, Edwards R, Pal R, Greaves P, Jariel-Encontre I, Piechaczyk M, Kriajevska M, Mellon JK, Dhillon AS, Tulchinsky E. Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL. Oncogene31:1493-503. doi: 10.1038/onc.2011.336 (2012).

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