ENAMPT/Ac-STAT3/DIRAS2 Axis Promotes Development and Cancer Stemness in Triple-Negative Breast Cancer by Enhancing Cytokine Crosstalk Between Tumor-Associated Macrophages and Cancer Cells.

ABSTRACT: The intricate relationship between tumor-associated macrophages (TAMs) and cancer cells is pivotal for carcinogenesis, with TAMs being integral to the tumor microenvironment (TME). This study explores the novel mechanisms by which TAMs regulate the progression of triple-negative breast cancer (TNBC) within the TME. Using a co-culture system and methodologies such as cytokine arrays, proteomics, and CRISPR-Cas9, we investigated the crosstalk between TAMs and TNBC cells. We found that high levels of CD163⁺ TAMs in TNBC tissues correlate with poor prognosis. TNBC cell-conditioned medium induces macrophage polarization towards the M2 phenotype, enhancing TNBC cell migration, invasion, and stemness through the secretion of extracellular nicotinamide phosphoribosyltransferase (eNAMPT)

SUBMITTER: Zhang L 

PROVIDER: S-EPMC11900821 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature