Research Information System
Scientific Reports, vol.16, no.1, 2026 (SCI-Expanded, Scopus)
In the complex landscape of cancer progression, the immune system shapes crucial interactions between tumor and immune cells. Understanding this dialogue is essential for elucidating how immune-derived cues trigger epithelial-mesenchymal transition (EMT)-like transcriptional changes, a fundamental process that drives tumor cell plasticity and facilitates aggressive phenotypes. Here, we investigated the crosstalk between M2 macrophages and colon cancer cells (HT-29) during the post-tumorigenic phase, focusing on exosome-mediated regulation of EMT, a critical pathway controlling tumor cell phenotypic and transcriptional dynamics. Co-culture experiments revealed that M2 macrophage–derived exosomes (M2-Exo) induced profound transcriptional changes, with downregulation of epithelial markers and increased expression of mesenchymal genes. Importantly, EMT induction was markedly stronger following M2-Exo treatment than in the co-culture setting, suggesting that while soluble mediators play a contributory role, EMT is predominantly and directly driven by exosome-mediated signaling. Transcriptomic profiling identified FAM83A as a key upregulated gene in M2-Exo–treated HT-29 cells. Functional analyses demonstrated that FAM83A promoted EMT by modulating regulators associated with decreased E-Cadherin and increased N-Cadherin, MMP2, and MMP9 expression. Importantly, siRNA-mediated silencing of FAM83A abolished its overexpression and inhibited EMT activation, confirming its essential role in M2-Exo–induced programming of EMT. Collectively, these findings highlight exosome-mediated immune-tumor interactions as critical drivers of EMT and the progression toward an invasive, mesenchymal-like phenotype.