Genomics

Dataset Information

0

Nuclear receptor RORγ is a targetable master regulator of cholesterol in a subtype of breast cancer [ChIP-Seq]


ABSTRACT: We show that triple-negative breast cancer (TNBC) exhibits a hyper-activated MVA-CB program that is strongly linked to nuclear receptor RORγ, compared to estrogen receptor-positive breast cancer. Genetic and pharmacological inhibition of RORγ reduces tumor cholesterol contents and synthesis rate while preserving host cholesterol homeostasis. We demonstrate, for the first time, that RORγ functions as a master activator of the entire MVA-CB program, dominantly over SREBP2, through its own direct binding and facilitating the recruitment of SREBP2. RORγ inhibition disrupts its association with SREBP2 and reduces MVA-CB chromatin acetylation. RORγ antagonists cause sustained TNBC tumor regression in patient-derived and immune-intact models. Their combination with cholesterol-lowering statins elicits superior anti-tumor synergy selectively in TNBC. Together, our studies uncover a previously unsuspected master regulator of MVA-CB and an attractive target for TNBC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE126380 | GEO | 2019/08/04

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2019-08-04 | GSE131856 | GEO
2024-01-01 | GSE242401 | GEO
2024-02-01 | GSE166520 | GEO
2023-05-17 | GSE230039 | GEO
2023-08-14 | GSE239740 | GEO
2024-01-24 | GSE234660 | GEO
2024-04-15 | GSE261067 | GEO
2022-02-08 | GSE184002 | GEO
| PRJNA545129 | ENA
2024-04-07 | GSE208160 | GEO