PLK1 signaling in breast cancer cells cooperates with estrogen receptor-dependent gene transcription

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  • dc.contributor.author Wierer, Michael, 1982-
  • dc.contributor.author Verde, Gaetano
  • dc.contributor.author Pisano, Paola
  • dc.contributor.author Molina, Henrik
  • dc.contributor.author Font Mateu, Jofre, 1977-
  • dc.contributor.author Di Croce, Luciano
  • dc.contributor.author Beato, Miguel
  • dc.date.accessioned 2025-02-03T07:43:11Z
  • dc.date.available 2025-02-03T07:43:11Z
  • dc.date.issued 2013
  • dc.description.abstract Polo-like kinase 1 (PLK1) is a key regulator of cell division and is overexpressed in many types of human cancers. Compared to its well-characterized role in mitosis, little is known about PLK1 functions in interphase. Here, we report that PLK1 mediates estrogen receptor (ER)-regulated gene transcription in human breast cancer cells. PLK1 interacts with ER and is recruited to ER cis-elements on chromatin. PLK1-coactivated genes included classical ER target genes such as Ps2, Wisp2, and Serpina3 and were enriched in developmental and tumor-suppressive functions. Performing large-scale phosphoproteomics of estradiol-treated MCF7 cells in the presence or absence of the specific PLK1 inhibitor BI2536, we identified several PLK1 end targets involved in transcription, including the histone H3K4 trimethylase MLL2, the function of which on ER target genes was impaired by PLK1 inhibition. Our results propose a mechanism for the tumor-suppressive role of PLK1 in mammals as an interphase transcriptional regulator.en
  • dc.description.sponsorship We would like to thank Thorsten Berg for kindly providing the Poloxin compound; Johan Staaf for the preprocessed 1,881-sample breast tumor data set; Giancarlo Castellano, Sarah Bonnin, and Andrew Pohl for bioinformatic support; Alessandra Ciociola and Roni Wright for experimental help; and Juan Valcarcel for critically reading the manuscript. Mass spectrometry, microarray, and cell sorting analyses were performed at the UPF/CRG proteomic, microarray, and flow cytometry core facilities, respectively. G.V. has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number 299429 and from the European Molecular Biology Organization (EMBO long-term fellowship ALTF 1106-2011, cofunded with the European Commission EMBOCOFUND2010, GA-2010-267146). This study was supported by grants from the Spanish government (BMC 2003-02902 and 2010-15313; CSD2006-00049), the European Union (IP HEROIC), and the Catalan government (AGAUR).en
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Wierer M, Verde G, Pisano P, Molina H, Font-Mateu J, Di Croce L, et al. PLK1 signaling in breast cancer cells cooperates with estrogen receptor-dependent gene transcription. Cell Rep. 2013 Jun;3(6):2021-32. DOI: 10.1016/j.celrep.2013.05.024
  • dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2013.05.024
  • dc.identifier.issn 2211-1247
  • dc.identifier.uri http://hdl.handle.net/10230/69433
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Cell Reports. 2013 Jun;3(6):2021-32
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/299429
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/CSD2006-00049
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BMC2010-15313
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PN/BMC2003-02902
  • dc.rights This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/
  • dc.subject.other Mama -- Càncerca
  • dc.subject.other Estrògens -- Receptorsca
  • dc.subject.other Mitosica
  • dc.title PLK1 signaling in breast cancer cells cooperates with estrogen receptor-dependent gene transcriptionen
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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