结直肠癌（CRC）的发展受一系列的基因和微环境变化的调节。Olfactomedin 4（OLFM4）是一种高表达于胃肠道并调节炎症的分泌性糖蛋白，然而它在CRC中的作用尚不确定。本研究旨在探讨OLFM4在CRC中的生物功能。OLFM4的mRNA表达在增生性病变和溃疡性结肠炎前期病变中上调，但在CRC中降低。OLFM4中和抗体抑制了AOM/DSS结肠相关癌症模型中的炎症介导的早期CRC形成。OLFM4敲低细胞在体内外表现出细胞增殖和运动的增加。OLFM4消融增加了异种移植实验中的肿瘤生长和转移。此外，OLFM4敲低细胞显示出结肠癌干细胞标记物CD133的上调，导致通过上皮间质转化信号通路的转移增加。本研究证明，OLFM4以不同的方式调节炎症和癌症进展；OLFM4的消融通过干细胞和上皮间质转化促进了癌症的转移。这些结果提供了控制癌症进展和转移的新途径。©2022.作者授权Springer Nature America，Inc.进行独家许可。

Development of colorectal cancer (CRC) is regulated by a series of genetic and microenvironmental alterations. Olfactomedin 4 (OLFM4) is a secreted glycoprotein that is highly expressed in the gastrointestinal tract and modulates inflammation. However, the role of OLFM4 in CRC is uncertain. Here we aimed to explore the function of OLFM4 in CRC in vivo and in vitro. The mRNA expression of OLFM4 was up-regulated in precursor lesions with dysplasia or ulcerative colitis but was reduced in CRC. OLFM4 neutralizing antibody suppressed inflammation-mediated early-stage CRC formation in an AOM/DSS colitis-associated cancer model. OLFM4 knockdown cells exhibited increased cell proliferation and motility in vitro and in vivo. Ablation of OLFM4 increased tumor growth and metastasis in xenograft experiments. In addition, OLFM4 knockdown cells showed elevated expression of colon cancer stem cell markers including CD133, resulting in increased metastasis via epithelial-mesenchymal transition signaling. This study demonstrated that OLFM4 regulates inflammation and cancer progression differently; ablation of OLFM4 promotes cancer metastasis via stemness and epithelial-mesenchymal transition. These results suggest a new route for controlling cancer progression and metastasis.© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.