Tumor cell-derived exosomal E2F7 promotes colorectal cancer progression by interacting with SMC4 and induced macrophage M2 polarization.

BACKGROUND: E2F7 regulates cell cycle progression and is overexpressed in multiple cancers, but its role in tumor, which macrophage crosstalk in colorectal cancer (CRC) remains unclear. METHODS: E2F7 expression in CRC was analyzed by qRT-PCR, Western blot, and immunohistochemistry. Functional studies used E2F7 knockdown, followed by assays for proliferation, apoptosis, migration, and invasion. Exosomes were isolated via ultracentrifugation, and their cargo analyzed. Macrophage polarization was assessed in vitro and in CRC mouse models. RESULTS: E2F7 was significantly upregulated in CRC and correlated with CD163+ macrophage infiltration. E2F7 silencing suppressed tumor cell growth, migration, and invasion, and reduced M2 macrophage polarization. CRC-derived exosomes transferred E2F7 to macrophages, where it bound SMC4 to induce an immunosuppressive M2-like phenotype. In vivo, E2f7 knockdown inhibited tumor growth and decreased M2 macrophages. CONCLUSION: Exosomal E2F7 from CRC cells promotes M2 macrophage polarization in an SMC4-dependent manner, revealing a novel tumor-immune communication axis that contributes to CRC progression.