库普弗细胞是肝组织中的巨噬细胞，对于检测和清除癌细胞至关重要。然而，它们的检测和癌细胞吞噬作用的分子机制仍不清楚。通过体内全基因组 CRISPR-Cas9 敲除筛选，我们发现在各种癌细胞上表达的细胞表面跨膜蛋白 ERMAP 可以激活 Kupffer 细胞的吞噬作用并控制肝转移。 ERMAP 与 Kupffer 细胞表面表达的 β-半乳糖苷结合凝集素 galectin-9 相互作用，其方式依赖于糖基化。 Galectin-9与ERMAP和Kupffer细胞上表达的跨膜受体dectin-2形成桥接复合物，诱导Kupffer细胞检测和吞噬癌细胞。肿瘤上ERMAP低表达的患者肝转移较多。因此，我们的研究确定 ERMAP-galectin-9-dectin-2 轴是库普弗细胞的“吃我”信号。© 2023。作者获得 Springer Nature America, Inc. 的独家许可。

Kupffer cells, the liver tissue resident macrophages, are critical in the detection and clearance of cancer cells. However, the molecular mechanisms underlying their detection and phagocytosis of cancer cells are still unclear. Using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that the cell-surface transmembrane protein ERMAP expressed on various cancer cells signaled to activate phagocytosis in Kupffer cells and to control of liver metastasis. ERMAP interacted with β-galactoside binding lectin galectin-9 expressed on the surface of Kupffer cells in a manner dependent on glycosylation. Galectin-9 formed a bridging complex with ERMAP and the transmembrane receptor dectin-2, expressed on Kupffer cells, to induce the detection and phagocytosis of cancer cells by Kupffer cells. Patients with low expression of ERMAP on tumors had more liver metastases. Thus, our study identified the ERMAP-galectin-9-dectin-2 axis as an 'eat me' signal for Kupffer cells.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.