Center of Reproductive Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China.
Department of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China.
Biochem Biophys Res Commun. 2018 Nov 17;506(1):243-250. doi: 10.1016/j.bbrc.2018.09.114. Epub 2018 Oct 19.
Although leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) is known as an immune inhibitory receptor to suppress the immune system, its function in cancer development remains largely unknown. Herein, we provide the first body of information showing that LILRB2 is highly expressed in the endometrial cancer. More importantly, the expression levels of LILRB2 are inversely correlated with the overall patients' survival. Knockdown of LILRB2 results in a dramatic decrease in the proliferation, colony formation and migration in several endometrial cancer cell lines in vitro. Furthermore, in vivo xenograft experiments reveal a notable reduction of tumor cell growth. Mechanistically, LILRB2 enhances the SHP2/CaMK1/CREB signaling pathways to support the expansion and migration of the endometrial cancer cells. These findings unravel an unexpected role of LILRB2 in solid cancers except for its canonical role in immune surveillance, which may serve as a potential endometrial stem cell marker and may benefit the development of novel strategies for the treatment of endometrial cancers.
尽管白细胞免疫球蛋白样受体亚家族 B 成员 2（LILRB2）被认为是一种免疫抑制受体，可抑制免疫系统，但它在癌症发展中的作用在很大程度上尚不清楚。在此，我们首次提供了信息，表明 LILRB2 在子宫内膜癌中高度表达。更重要的是，LILRB2 的表达水平与患者的总生存呈负相关。LILRB2 的敲低导致几种子宫内膜癌细胞系在体外的增殖、集落形成和迁移能力显著下降。此外，体内异种移植实验显示肿瘤细胞生长明显减少。从机制上讲，LILRB2 增强了 SHP2/CaMK1/CREB 信号通路，以支持子宫内膜癌细胞的扩增和迁移。这些发现揭示了 LILRB2 在实体瘤中的作用除了其在免疫监视中的典型作用之外，它可能作为一种潜在的子宫内膜干细胞标志物，并可能有益于开发治疗子宫内膜癌的新策略。
