Targeting TAF1 with BAY-299 induces antitumor immunity in triple-negative breast cancer.
Biochem Biophys Res Commun
; 665: 55-63, 2023 07 12.
Article
em En
| MEDLINE
| ID: mdl-37148745
ABSTRACT
Triple-negative breast cancer (TNBC) is a heterogeneous breast cancer subtype with poor prognoses and limited therapeutic options. The TATA-box binding protein associated factor 1 (TAF1) is an essential protein involved in the transcriptional regulation of cancer development and progress. However, the therapeutic potential and underlying mechanism of targeting TAF1 in TNBC remain unknown. Here, using chemical probe BAY-299, we identify that TAF1 inhibition leads to the induction of endogenous retrovirus (ERVs) expression and double-stranded RNA (dsRNA) formation, resulting in the activation of interferon responses and cell growth suppression in a subset of TNBC, resembling anti-viral mimicry effect. This correlation between TAF1 and interferon signature was validated in three independent breast cancer patient datasets. Furthermore, we observe heterogeneous responses to TAF1 inhibition across a set of TNBC cell lines. By integrating transcriptome and proteome data, we demonstrate that high levels of proliferating cell nuclear antigen (PCNA) protein serve as a predictive biomarker associated with suppressive tumor immune responses in various cancers, which may limit the efficiency of TAF1 inhibition.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias de Mama Triplo Negativas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article