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  • Michels, JudithEquipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France (author)

MCL-1 dependency of cisplatin-resistant cancer cells

  • Article/chapterEnglish2014

Publisher, publication year, extent ...

  • Elsevier,2014
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:umu-199928
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-199928URI
  • https://doi.org/10.1016/j.bcp.2014.07.029DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Part of the Special Issue: Metabolism 2014 – Alterations of metabolic pathways as therapeutic targets
  • The selection of human cancer cell lines in cis-diamminedichloroplatinum(II) (CDDP, best known as cisplatin) is accompanied by stereotyped alterations that contribute to the acquisition of a CDDP-resistant state. Thus, CDDP resistance often leads to the upregulation of the DNA repair enzyme poly (ADP-ribose) polymerase-1 (PARP1) with the consequent intracellular accumulation of poly (ADP-ribose) (PAR)-modified proteins. Here we report another frequent alteration accompanying CDDP resistance, namely upregulation of the antiapoptotic BCL-2 family protein MCL-1. Six out of 8 CDDP resistant cancer cell lines manifested an increase in MCL-1 protein expression level, while only a minority of cell lines overexpressed BCL-2 or BCL-XL. BCL-XL was decreased in six out of 8 cancer cell lines. Importantly, MCL-1 overexpressing, CDDP resistant cells appear to be 'addicted' to MCL-1 because they died upon depletion of MCL-1 by RNA interference or pharmacological inhibition of MCL-1 expression by the BH3 mimetic obatoclax. Knockdown of PARP1 did not succeed in reducing MCL-1 expression, while depletion or inhibition of MCL-1 failed to affect the activity of PARP1. Hence, the two resistance mechanisms are not linked to each other by a direct cause-effect relationship. Importantly, CDDP-resistant, MCL-1 overexpressing human non-small cell lung cancers responded to monotherapy with obatoclax in vivo, in xenotransplanted mice, underscoring the probable therapeutic relevance of these findings.

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  • Obrist, FlorineEquipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France; Université Paris Sud, Villejuif, France (author)
  • Vitale, IlioRegina Elena National Cancer Institute, Rome, Italy (author)
  • Lissa, DelphineEquipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France (author)
  • Garcia, PaulineEquipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France (author)
  • Behnam-Motlagh, ParvizUmeå universitet,Klinisk kemi(Swepub:umu)pabe0001 (author)
  • Kohno, KimitoshiDepartment of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan (author)
  • Wu, Gen ShengDepartment of Oncology and Pathology, School of Medicine, Wayne State University, MI, Detroit, United States (author)
  • Brenner, CatherineU769, INSERM-LabEx LERMIT, Faculté de Pharmacie, Châtenay Malabry, France (author)
  • Castedo, MariaEquipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France (author)
  • Kroemer, GuidoEquipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France (author)
  • Equipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, FranceEquipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France; Université Paris Sud, Villejuif, France (creator_code:org_t)

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  • In:Biochemical Pharmacology: Elsevier92:1, s. 55-610006-29521356-1839

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