Epigenomic disorder and partial EMT impair luminal progenitor integrity in Brca1-associated breast tumorigenesis.

ABSTRACT: In breast cancer related to the BRCA1 mutation, luminal progenitor cells are believed to be the cells of origin, yet how these cells transform into invasive cancer cells remain poorly understood. Here, we combine single-cell epigenomic and transcriptomic data to reconstitute sequences of events in luminal cells that lead to tumorigenesis. Upon deletion of Trp53 and Brca1, we find that luminal progenitors display an extensive epigenomic disorder associated with a loss of cell identity. These cells then progress to tumor formation through a partial epithelial-to-mesenchymal transition, orchestrated by Snail and the timely activation of immunosuppressive and FGF signaling with their microenvironment. In human samples, pre-tumoral changes can be detected in early stage, basal-like tumors, whic

SUBMITTER: Landragin C 

PROVIDER: S-EPMC12036258 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature