EYA3 regulation of NF-κB and CCL2 suppresses cytotoxic NK cells in the premetastatic niche to promote TNBC metastasis.

ABSTRACT: Triple-negative breast cancer cells must evade immune surveillance to metastasize to distant sites, yet this process is not well understood. The Eyes absent (EYA) family of proteins, which are crucial for embryonic development, become dysregulated in cancer, where they have been shown to mediate proliferation, migration, and invasion. Our study reveals an unusual mechanism by which EYA3 reduces the presence of cytotoxic natural killer (NK) cells in the premetastatic niche (PMN) to enhance metastasis, independent of its effects on the primary tumor. We find that EYA3 up-regulates nuclear factor κB signaling to enhance CCL2 expression, which, in contrast to previous findings, suppresses cytotoxic NK cell activation in vitro and their infiltration into the PMN in vivo. These findings uncover

SUBMITTER: Rosenbaum SR 

PROVIDER: S-EPMC12057687 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature