Here, we found through transcriptional profiling that the MGAT5 gene is a key regulator of anoikis resistance in colon cancer, and that the lectin from Sambucus sieboldiana (SSA) efficiently sensitized colon cancer cells to anoikis in vitro and in vivo: MGAT catalyzed the formation of the pro-metastatic a β1,6-GlcNAc linkage of N-glycan, and SSA interfered with the pro-metastatic action of the glycan linkage in cancer cells. Here, MGAT5 is linked to colonic neoplasm.