Mediator Subunit Med4 Enforces Metastatic Dormancy in Breast Cancer.

ABSTRACT: Long term survival of breast cancer patients is limited due to recurrence from metastatic dormant cancer cells. However, the mechanisms by which these dormant breast cancer cells survive and awaken remain poorly understood. Our unbiased genome-scale genetic screen in mice identified Med4 as a novel cancer-cell intrinsic gatekeeper in metastatic reactivation. MED4 haploinsufficiency is prevalent in metastatic breast cancer patients and correlates with poorer prognosis. Syngeneic xenograft models revealed that Med4 enforces breast cancer dormancy. Contrary to the canonical function of the Mediator complex in activating gene expression, Med4 maintains 3D chromatin compaction and enhancer landscape, by preventing enhancer priming or activation through the suppressio

SUBMITTER: Bae SY 

PROVIDER: S-EPMC10680920 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature