<i>In vitro</i>, STC1 promoted M2 macrophage polarization, while M2 macrophages enhanced EMT and metastatic traits of CRC cells, supporting a pro-tumor positive-feedback loop.<h4>Conclusion</h4>STC1 facilitates CRC invasion and migration by activating TGF-β1/Smad signaling and driving M2 macrophage polarization, suggesting its utility as a prognostic biomarker and therapeutic target. The gene discussed is TGFB1; the disease is neoplasm.