Hypoxic cancer-associated fibroblast exosomal circSTAT3 drives triple negative breast cancer stemness via miR-671-5p/NOTCH1 signaling.

ABSTRACT:

Background

The hypoxic tumor microenvironment, particularly hypoxia-conditioned cancer-associated fibroblasts (CAFs), drives breast cancer (BC) progression and therapy resistance. However, the molecular mechanisms linking hypoxic CAFs to BC plasticity and chemoresistance remain elusive.

Methods

Primary CAFs were isolated from high-grade BC tissues (Grade III) and characterized (α-SMA⁺/CD34⁻/pan-CK⁻), with normal fibroblasts (NFs) from reduction mammoplasty as controls. Hypoxic CAF-derived exosomal circSTAT3 stability was validated using RNase R resistance and actinomycin D assays. Exosomes were characterized via transmission electron microscopy (TEM), dynamic light scattering (DLS), and marker profiling (CD63⁺/TSG101⁺/Alix⁺, calnexin⁻). Functional effects of hypoxic CAF exos

SUBMITTER: Yang L 

PROVIDER: S-EPMC12288262 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature