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

Autor: Laura Pascual‐Reguant, Queralt Serra‐Camprubí, 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‐Ropero, Joaquin Arribas, Violeta Serra, Luis Serrano, Tian V Tian, Sandra Peiró, Sara Sdelci
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 15, Iss 12, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 1757-4684
1757-4676
DOI: 10.15252/emmm.202318459
Popis: 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 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.
Databáze: Directory of Open Access Journals
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