TLE3 Sustains Luminal Breast Cancer Lineage Fidelity to Suppress Metastasis.

ABSTRACT: Breast cancer subtypes and their phenotypes parallel different stages of the mammary epithelial cell developmental hierarchy. Discovering mechanisms that control lineage identity could provide novel avenues for mitigating disease progression. Here we report that the transcriptional corepressor TLE3 is a guardian of luminal cell fate in breast cancer and operates independently of the estrogen receptor. In luminal breast cancer, TLE3 actively repressed the gene-expression signature associated with highly aggressive basal-like breast cancers (BLBC). Moreover, maintenance of the luminal lineage depended on the appropriate localization of TLE3 to its transcriptional targets, a process mediated by interactions with FOXA1. By repressing genes that drive BLBC phenotypes, including SOX9 and TGFβ2,

SUBMITTER: Anstine LJ 

PROVIDER: S-EPMC10089698 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature