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PML hyposumoylation is responsible for the resistance of pancreatic cancer
Mirna Swayden
1
George Alzeeb
1
Rawand Masoud
1
Yolande Berthois
1
Stéphane Audebert
1
Luc Camoin
1
Laurent Hannouche
2
Hortense Vachon
2
Odile Gayet
1
Martin Bigonnet
1
Julie Roques
1
Françoise Silvy
1
Alice Carrier
1
Nelson Dusetti
1
Juan Iovanna
1
Philippe Soubeyran
1, *
*
Corresponding author
Stéphane Audebert 1
Mail :
Author IdHAL : stephane-audebert ORCID : https://orcid.org/0000-0002-9409-2588
Luc Camoin 1
Mail :
Author IdHAL : camoin-luc ORCID : https://orcid.org/0000-0002-1230-4787
Laurent Hannouche 2
Author
Hortense Vachon 2
Mail :
Author IdHAL : hortense-vachon
Alice Carrier 1
Author
Nelson Dusetti 1
Author
Juan Iovanna 1
Mail :
Author
Philippe Soubeyran 1
Mail :
Correspondent author
1
CRCM - Centre de Recherche en Cancérologie de Marseille (27 bd Leï Roure, BP 300059
13273 Marseille Cedex 09 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR7258 (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1068 (101, rue de Tolbiac, 75013 Paris - France)
- Institut Paoli-Calmettes : UMR7258 (France)
- AMU - Aix Marseille Université : UM105 (Aix-Marseille Université Jardins du Pharo 58 Boulevard Charles Livon 13284 Marseille cedex 7 - France)
2
TAGC - Theories and Approaches of Genomic Complexity (Parc scientifique de Luminy - 163 avenue de Luminy 13288 Marseille cedex 9 - France)
- AMU - Aix Marseille Université (Aix-Marseille Université Jardins du Pharo 58 Boulevard Charles Livon 13284 Marseille cedex 7 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1090 (101, rue de Tolbiac, 75013 Paris - France)
Abstract : The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is mainly due to its rapidly acquired resistance to all conventional treatments. Despite drug-specific mechanisms of resistance, none explains how these cells resist the stress induced by any kind of anticancer treatment. Activation of stress-response pathways relies on the post-translational modifications (PTMs) of involved proteins. Among all PTMs, those mediated by the ubiquitin family of proteins play a central role. Our aim was to identify alterations of ubiquitination, neddylation, and sumoylation associated with the multiresistant phenotype and demonstrate their implications in the survival of PDAC cells undergoing treatment. This approach pointed at an alteration of promyelocytic leukemia (PML) protein sumoylation associated with both gemcitabine and oxaliplatin resistance. We could show that this alteration of PML sumoylation is part of a general mechanism of drug resistance, which in addition involves the abnormal activation of NF-kB and cAMP response element binding pathways. Importantly, using patient-derived tumors and cell lines, we identified a correlation between the levels of PML expression and sumoylation and the sensitivity of tumors to anticancer treatments.-Swayden, M.
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Journal articles
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https://www.hal.inserm.fr/inserm-02439811
Contributor : Philippe Soubeyran <>
Submitted on : Tuesday, January 14, 2020 - 5:53:41 PM
Last modification on : Tuesday, March 3, 2020 - 2:10:21 PM
Contributor : Philippe Soubeyran <>
Submitted on : Tuesday, January 14, 2020 - 5:53:41 PM
Last modification on : Tuesday, March 3, 2020 - 2:10:21 PM
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Identifiers
- HAL Id : inserm-02439811, version 1
- DOI : 10.1096/fj.201901091R
- PUBMED : 31557059
- PUBMEDCENTRAL : PMC6902661
Citation
Mirna Swayden, George Alzeeb, Rawand Masoud, Yolande Berthois, Stéphane Audebert, et al.. PML hyposumoylation is responsible for the resistance of pancreatic cancer. FASEB Journal, Federation of American Society of Experimental Biology, 2019, 33 (11), pp.12447-12463. ⟨10.1096/fj.201901091R⟩. ⟨inserm-02439811⟩
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