Immunoglobulin-like transcript 4 and human leukocyte antigen-G interaction promotes the progression of human colorectal cancer
Immunoglobulin-like transcript 4 and human leukocyte antigen-G interaction promotes the progression of human colorectal cancer
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DOI：
10.3892/ijo.2019.4761
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发表时间：
2019-06-01
影响因子：
5.2
通讯作者：
Yu, Shuwen
中科院分区：
文献类型：
--
作者：
Cai, Zhaoyang;Wang, Lu;Yu, Shuwen
免疫球蛋白样转录本（Immunocytulin-like transcript，ILT）4是一种免疫应答负调控因子，在移植排斥、自身免疫和感染性疾病中发挥重要作用。本研究揭示了IL-4和人类白细胞抗原G（human leukocyte antigen G，HLA-G）在人原发性结直肠癌（primary colorectal cancer，CRC）组织中的共表达，并探讨了其与年龄、分期、淋巴结转移和总生存期的关系。在结直肠癌细胞系中，ILT 4和HLA-G共表达及其自分泌调节被证实。ILT 4干扰可影响HLA-G的表达，调节大肠癌细胞的增殖、侵袭和迁移。HLA-G融合蛋白处理还以剂量依赖性方式增加ILT 4表达，从而激活蛋白激酶B（AKT）和细胞外信号调节激酶（ERK）信号传导，并促进CRC细胞的增殖、迁移和侵袭。此外，阻断ILT 4可抑制HLA-G诱导的AKT和ERK活化以及CRC细胞恶性特征。本研究结果提示ILT 4与HLA-G相互作用通过激活AKT和ERK信号促进CRC进展，为阻断ILT 4/HLA-G治疗CRC提供了新的策略。
Immunoglobulin like transcript (ILT) 4, a negative regulator of immune response in allograft rejection, autoimmunity and infectious diseases, has recently been determined to serve important roles in tumor development. In the present study, the co expression of ILT4 and human leukocyte antigen G (HLA-G) in tissues of human primary colorectal cancer (CRC) was revealed, and its association with older age, advanced stage, regional lymph node involvement and poor overall survival time was identified. In CRC cell lines, ILT4 and HLA-G co expression and their autocrine regulation was demonstrated. ILT4 interference affected HLA-G expression and regulated the cell proliferation, invasion and migration of CRC. HLA-G fusion protein treatment also increased ILT4 expression in a dose dependent manner, thereby activating protein kinase B (AKT) and extracellular signal regulated kinase (ERK) signaling, and facilitating the proliferation, migration and invasion of CRC cells. Additionally, the AKT and ERK activation, and CRC cell malignant characteristics induced by HLA-G may be suppressed by blocking ILT4. The present results indicated that the interaction of ILT4 and its ligand HLA-G promotes CRC progression through AKT and ERK signal activation, providing a novel strategy of blocking ILT4/HLA-G for the treatment of CRC.