FAT1 functions as an oncogenic driver in triple negative breast cancer through AKT pathway-driven effects on the matrisome.

ABSTRACT: FAT1 cadherin exhibits dual tumor suppressor and oncogenic roles across various cancers, but its function in breast cancer remains unclear due to conflicting reports of mutational loss and overexpression. In this study, we demonstrate that FAT1 mRNA and protein levels are reduced during mammary transformation, an effect linked to promoter methylation rather than mutational events. Subtype-specific analysis reveals that high FAT1 expression correlates with poor outcomes in basal-like/triple-negative breast cancer (TNBC), while elevated FAT1 expression in luminal A/estrogen receptor-positive breast cancers is associated with improved patient prognosis. Functional studies in TNBC models using knockdown and overexpression approaches confirm that FAT1 promotes both cell proliferation and motili

SUBMITTER: Zhao P 

PROVIDER: S-EPMC11900804 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature