RAD51B-EZH2 axis as a potential therapeutic target for TNBC through cell fate conversion.

ABSTRACT: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with higher histologic grade, poorer prognosis, and fewer treatment options due to the lack of reliable and effective molecular targets. Using a functional approach with the Sleeping Beauty (SB) transposon system, we have identified 64 overlapped candidate driver genes for inducing TNBC formation in Brca1-deficient mice and Fgfr2-mutant mice. Further analysis reveals that Rad51b deficiency leads to the development of tumors with a TNBC phenotype by repressing ERα expression through the recruitment of polycomb repressive complex 2 (PRC2) and subsequent trimethylation of histone H3 lysine 27 in Esr1 promoter region. Mechanistically, the loss of RAD51B upregulated cellular ATP levels, followed by the suppress

SUBMITTER: Lin S 

PROVIDER: S-EPMC12827460 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature