Time-Resolved Profiling Reveals ATF3 as a Novel Mediator of Endocrine Resistance in Breast Cancer.
ATF3
RPPA
breast cancer
drug-resistance
endocrine therapy
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
11 Oct 2020
11 Oct 2020
Historique:
received:
19
08
2020
revised:
29
09
2020
accepted:
07
10
2020
entrez:
14
10
2020
pubmed:
15
10
2020
medline:
15
10
2020
Statut:
epublish
Résumé
Breast cancer is one of the leading causes of death for women worldwide. Patients whose tumors express Estrogen Receptor α account for around 70% of cases and are mostly treated with targeted endocrine therapy. However, depending on the degree of severity of the disease at diagnosis, 10 to 40% of these tumors eventually relapse due to resistance development. Even though recent novel approaches as the combination with CDK4/6 inhibitors increased the overall survival of relapsing patients, this remains relatively short and there is a urgent need to find alternative targetable pathways. In this study we profiled the early phases of the resistance development process to uncover drivers of this phenomenon. Time-resolved analysis revealed that ATF3, a member of the ATF/CREB family of transcription factors, acts as a novel regulator of the response to therapy via rewiring of central signaling processes towards the adaptation to endocrine treatment. ATF3 was found to be essential in controlling crucial processes such as proliferation, cell cycle, and apoptosis during the early response to treatment through the regulation of MAPK/AKT signaling pathways. Its essential role was confirmed in vivo in a mouse model, and elevated expression of
Identifiants
pubmed: 33050633
pii: cancers12102918
doi: 10.3390/cancers12102918
pmc: PMC7650760
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : EpiPredict - 642691
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