title: PLK1 signaling in breast cancer cells cooperates with estrogen receptor-dependent gene transcription.
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.
authors.affiliation: Gene Regulation Stem Cells and Cancer Program, Center for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Michael
authors.initials: M
authors.lastname: Wierer
authors.forename: Gaetano
authors.initials: G
authors.lastname: Verde
authors.forename: Paola
authors.initials: P
authors.lastname: Pisano
authors.forename: Henrik
authors.initials: H
authors.lastname: Molina
authors.forename: Jofre
authors.initials: J
authors.lastname: Font-Mateu
authors.forename: Luciano
authors.initials: L
authors.lastname: Di Croce
authors.forename: Miguel
authors.initials: M
authors.lastname: Beato
mesh_terms: D001549:Benzamides / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006574:Heterocyclic Compounds, 2-Ring / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011621:Pteridines; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D000097869:Polo-Like Kinase 1
chemical_list: D001549:Benzamides; D018797:Cell Cycle Proteins; D002843:Chromatin; D006574:Heterocyclic Compounds, 2-Ring; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D011960:Receptors, Estrogen; D000097869:Polo-Like Kinase 1; C518477:BI 2536