BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression.
Breast cancer
Cancer prevention
Journal
NPJ breast cancer
ISSN: 2374-4677
Titre abrégé: NPJ Breast Cancer
Pays: United States
ID NLM: 101674891
Informations de publication
Date de publication:
2020
2020
Historique:
received:
14
11
2019
accepted:
04
03
2020
entrez:
1
5
2020
pubmed:
1
5
2020
medline:
1
5
2020
Statut:
epublish
Résumé
The molecular processes by which some human ductal carcinoma in situ (DCIS) lesions advance to the more aggressive form, while others remain indolent, are largely unknown. Experiments utilizing a patient-derived (PDX) DCIS Mouse INtraDuctal (MIND) animal model combined with ChIP-exo and RNA sequencing revealed that the formation of protein complexes between B Cell Lymphoma-9 (BCL9), phosphoserine 727 STAT3 (PS-727-STAT3) and non-STAT3 transcription factors on chromatin enhancers lead to subsequent transcription of key drivers of DCIS malignancy. Downregulation of two such targets, integrin β3 and its associated metalloproteinase, MMP16, resulted in a significant inhibition of DCIS invasive progression. Finally, in vivo targeting of BCL9, using rosemary extract, resulted in significant inhibition of DCIS malignancy in both cell line and PDX DCIS MIND animal models. As such, our studies provide compelling evidence for future testing of rosemary extract as a chemopreventive agent in breast cancer.
Identifiants
pubmed: 32352029
doi: 10.1038/s41523-020-0157-z
pii: 157
pmc: PMC7181646
doi:
Types de publication
Journal Article
Langues
eng
Pagination
12Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM130423
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA207445
Pays : United States
Informations de copyright
© The Author(s) 2020.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing interests.
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