Kim Su-Man, Kim Eun-Mi, Ji Kon-Young, Lee Hwa-Youn, Yee Su-Min, Woo Su-Min, Yi Ja-Woon, Yun Chul-Ho, Choi Harim, Kang Hyung-Sik
School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Korea.
Korea Institute of Toxicology, Daejeon, 34114, Korea.
Cancers (Basel). 2019 Sep 6;11(9):1315. doi: 10.3390/cancers11091315.
TREM2 (triggering receptor expressed on myeloid cells) is involved in the development of malignancies. However, the function of TREM2 in colorectal cancer has not been clearly elucidated. Here, we investigated TREM2 function for the first time in colorectal epithelial cancer cells and demonstrated that TREM2 is a novel tumor suppressor in colorectal carcinoma. Blockade of TREM2 significantly promoted the proliferation of HT29 colorectal carcinoma cells by regulating cell cycle-related factors, such as p53 phosphorylation and p21 and cyclin D1 protein levels. HT29 cell migration was also increased by TREM2 inhibition via MMP9 (matrix metalloproteinase 9) expression upregulation. Furthermore, we found that the tumor suppressor effects of TREM2 were associated with Wnt/-catenin and extracellular signal-regulated kinase (ERK) signaling. Importantly, the effect of TREM2 in the suppression of tumor development was demonstrated by in vivo and in vitro assays, as well as in human colon cancer patient tissue arrays. Overall, our results identify TREM2 as a potential prognostic biomarker and therapeutic target for colorectal cancer.
触发受体表达于髓样细胞2（TREM2）参与恶性肿瘤的发生发展。然而，TREM2在结直肠癌中的功能尚未明确阐明。在此，我们首次在结直肠癌细胞中研究了TREM2的功能，并证明TREM2是结直肠癌中的一种新型肿瘤抑制因子。阻断TREM2通过调节细胞周期相关因子，如p53磷酸化以及p21和细胞周期蛋白D1的蛋白水平，显著促进HT29结直肠癌细胞的增殖。通过上调基质金属蛋白酶9（MMP9）的表达，抑制TREM2也会增加HT29细胞的迁移。此外，我们发现TREM2的肿瘤抑制作用与Wnt/β-连环蛋白和细胞外信号调节激酶（ERK）信号通路有关。重要的是，体内和体外实验以及人类结肠癌患者组织芯片均证实了TREM2在抑制肿瘤发展方面的作用。总体而言，我们的研究结果表明TREM2是结直肠癌潜在的预后生物标志物和治疗靶点。
