CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression.
Journal
Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086
Informations de publication
Date de publication:
02 02 2022
02 02 2022
Historique:
entrez:
2
2
2022
pubmed:
3
2
2022
medline:
7
4
2022
Statut:
ppublish
Résumé
Metastasis is the major cause of cancer-related deaths due to the lack of effective therapies. Emerging evidence suggests that certain epigenetic and transcriptional regulators drive cancer metastasis and could be targeted for metastasis treatment. To identify epigenetic regulators of breast cancer metastasis, we profiled the transcriptomes of matched pairs of primary breast tumors and metastases from human patients. We found that distant metastases are more immune inert with increased M2 macrophages compared to their matched primary tumors. The acetyl-lysine reader, cat eye syndrome chromosome region candidate 2 (CECR2), was the top up-regulated epigenetic regulator in metastases associated with an increased abundance of M2 macrophages and worse metastasis-free survival. CECR2 was required for breast cancer metastasis in multiple mouse models, with more profound effect in the immunocompetent setting. Mechanistically, the nuclear factor κB (NF-κB) family member v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA) recruits CECR2 to increase chromatin accessibility and activate the expression of their target genes. These target genes include multiple metastasis-promoting genes, such as
Identifiants
pubmed: 35108062
doi: 10.1126/scitranslmed.abf5473
pmc: PMC9003667
mid: NIHMS1793345
doi:
Substances chimiques
CECR2 protein, mouse
0
Cecr2 protein, human
0
NF-kappa B
0
Transcription Factor RelA
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabf5473Subventions
Organisme : NCI NIH HHS
ID : P30 CA016359
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA191548
Pays : United States
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