Pascual-Reguant, Laura, 1990-Datta, DebayanCianferoni, DamianoKourtis, SavvasGañez-Zapater, AntoniCannatá, ChiaraEspinar, LorenaGarcía López, LauraMusa-Afaneh, SaraGuirola, MariaGkanogiannis, AnestisMiró Canturri, AndreaArribas, JoaquínSerrano Pubull, Luis, 1982-Sdelci, Sara2024-02-082024-02-082023Pascual-Reguant L, Serra-Camprubí Q, Datta D, Cianferoni D, Kourtis S, Gañez-Zapater A et al. Interactions between BRD4S, LOXL2, and MED1 drive cell cycle transcription in triple-negative breast cancer. EMBO Mol Med. 2023 Dec 7;15(12):e18459. DOI: 10.15252/emmm.2023184591757-4676http://hdl.handle.net/10230/58994Triple-negative breast cancer (TNBC) often develops resistance to single-agent treatment, which can be circumvented using targeted combinatorial approaches. Here, we demonstrate that the simultaneous inhibition of LOXL2 and BRD4 synergistically limits TNBC proliferation in vitro and in vivo. Mechanistically, LOXL2 interacts in the nucleus with the short isoform of BRD4 (BRD4S), MED1, and the cell cycle transcriptional regulator B-MyB. These interactions sustain the formation of BRD4 and MED1 nuclear transcriptional foci and control cell cycle progression at the gene expression level. The pharmacological co-inhibition of LOXL2 and BRD4 reduces BRD4 nuclear foci, BRD4-MED1 colocalization, and the transcription of cell cycle genes, thus suppressing TNBC cell proliferation. Targeting the interaction between BRD4S and LOXL2 could be a starting point for the development of new anticancer strategies for the treatment of TNBC.application/pdfeng© 2023 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/articlehttp://dx.doi.org/10.15252/emmm.202318459Cell cycleCombinatorial therapyGene expressionTriple-negative breast cancerinfo:eu-repo/semantics/openAccess