We found that TREM2 inhibited the canonical Wnt1/β-catenin signaling pathway (Figure 3), which in turn suppressed the proliferation and tumorigenicity of HT29 colon cancer cells (Figure 1) by inhibiting β-catenin/TCF4 transactivation activity (Figure 3E), resulting in the suppression of cell proliferation and DNA synthesis (Figure 1A–C). Here, TREM2 is linked to colonic neoplasm.