免疫球蛋白超家族（IgSF）成员EWI2的实验研究表明，它可以抑制动物模型中的多种实体恶性肿瘤，包括脑、肺、皮肤和前列腺癌，并且可以在体外抑制肿瘤细胞的运动和生长。虽然EWI2似乎在小鼠模型中支持骨髓性白血病，并维持白血病干细胞。生物信息学分析表明，EWI2基因表达在胶质母细胞瘤中下调，在黑色素瘤、胰腺癌和肝癌中上调。EWI2的作用机制与其抑制生长因子受体和细胞黏附蛋白有关，通过其关联的四跨膜富集膜结构域（TEMDs），改变这些跨膜蛋白的细胞表面聚集和内溶酶体的转运/代谢。最近的研究还表明，EWI2可以调节ERK和TFEB的核转位，改变这些基因表达调控因子的活性。对于包括FPRP、IgSF3和CD101在内的EWI2亲属，虽然他们在恶性疾病中的作用尚不明确，但FPRP和IgSF3可能促进实体恶性肿瘤的进展，而CD101似乎调节肿瘤微环境中的免疫细胞。与其他肿瘤调节因子不同，EWI亚家族成员对实体恶性肿瘤的影响可能是上下文依赖的。换句话说，一个给定的EWI亚家族成员对肿瘤的影响可能取决于该肿瘤中的分子网络和TEMD组成。总体而言，EWI2及其亲属已经成为恶性疾病的重要调节因子，具有有望成为抗癌治疗和癌症治疗靶点的潜力。©2023作者（s），独家许可Springer Nature Limited。

Experimental studies on immunoglobulin superfamily (IgSF) member EWI2 reveal that it suppresses a variety of solid malignant tumors including brain, lung, skin, and prostate cancers in animal models and inhibits tumor cell movement and growth in vitro. While EWI2 appears to support myeloid leukemia in mouse models and maintain leukemia stem cells. Bioinformatics analyses suggest that EWI2 gene expression is downregulated in glioblastoma but upregulated in melanoma, pancreatic cancer, and liver cancer. The mechanism of action for EWI2 is linked to its inhibition of growth factor receptors and cell adhesion proteins through its associated tetraspanin-enriched membrane domains (TEMDs), by altering the cell surface clustering and endolysosome trafficking/turnover of these transmembrane proteins. Recent studies also show that EWI2 modulates the nuclear translocation of ERK and TFEB to change the activities of these gene expression regulators. For EWI2 relatives including FPRP, IgSF3, and CD101, although their roles in malignant diseases are not fully clear and remain to be determined experimentally, FPRP and IgSF3 likely promote the progression of solid malignant tumors while CD101 seems to modulate immune cells of tumor microenvironment. Distinctive from other tumor regulators, the impacts of EWI subfamily members on solid malignant tumors are likely to be context dependent. In other words, the effect of a given EWI subfamily member on a tumor probably depends on the molecular network and composition of TEMDs in that tumor. Collectively, EWI2 and its relatives are emerged as important regulators of malignant diseases with promising potentials to become anti-cancer therapeutics and cancer therapy targets.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.