Interactions between BRD4S, LOXL2, and MED1 drive cell cycle transcription in triple‐negative breast cancer

• DOI: 10.15252/emmm.202318459
• Publication Date: 2023-11-08T11:01:02Z
• Authors: Laura Pascual‐Reg...; Queralt Serra‐Cam...; Debayan Datta; Damiano Cianferoni; Savvas Kourtis; Antoni Gañez‐Zapater; Chiara Cannatá; Lorena Espinar; Jessica Querol; Laura García‐López; Sara Musa‐Afaneh; Maria Guirola; Anestis Gkanogiannis; Andrea Miró Canturri; Marta Guzman; Olga Rodríguez; Andrea Herencia‐R...; Joaquin Arribas; Violeta Serra; Luis Serrano; Tian V Tian; Sandra Peiró; Sara Sdelci
• Keywords: Triple-negative breast cancer; BRD4

Abstract Triple‐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 vivo . Mechanistically, interacts nucleus with short isoform (BRD4S), MED1, cell cycle transcriptional regulator B‐MyB. These interactions sustain formation MED1 nuclear foci control progression at gene expression level. The pharmacological co‐inhibition reduces foci, BRD4‐MED1 colocalization, transcription genes, thus suppressing proliferation. Targeting interaction between BRD4S could a starting point for development new anticancer strategies treatment TNBC.