Lectin-like oxidized low-density lipoprotein receptor-1 facilitates metastasis of gastric cancer through driving epithelial-mesenchymal transition and PI3K/Akt/GSK3β activation.
Lectin-like oxidized low-density lipoprotein receptor-1 facilitates metastasis of gastric cancer through driving epithelial-mesenchymal transition and PI3K/Akt/GSK3β activation.
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DOI：
10.1038/srep45275
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发表时间：
2017-03-27
影响因子：
4.6
通讯作者：
Gu J
中科院分区：
文献类型：
--
作者：
Li C;Zhang J;Wu H;Li L;Yang C;Song S;Peng P;Shao M;Zhang M;Zhao J;Zhao R;Wu W;Ruan Y;Wang L;Gu J
凝集素样氧化低密度脂蛋白受体-1（LOX-1）是一种模式识别受体，在血管疾病和宿主免疫应答中起着关键作用。近年来，我们的研究发现LOX-1可通过与热休克蛋白结合，促进垂死细胞的摄取和细胞抗原的交叉提呈，与胃肿瘤的发生密切相关。因此，我们推测LOX-1可能作为一个癌基因在胃癌（GC）的发展和进展。本研究通过免疫组化染色和肿瘤相关数据库发现LOX-1在胃癌组织中表达上调，与胃癌患者预后不良相关。LOX-1的表达是影响胃癌患者OS的独立预后因素，LOX-1与胃癌TNM分期的结合更能准确预测胃癌患者的预后。体外transwell实验和western blot分析证实LOX-1可通过激活PI 3 K/Akt/GSK 3 β和促进上皮-间质转化促进胃癌细胞的迁移和侵袭。综上所述，我们首先探讨了LOX-1在GC中的表达谱、临床意义和生物学功能，这些数据表明LOX-1可能代表GC的有希望的预后生物标志物，并为GC治疗提供新的分子靶点。
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a pattern recognition receptor that plays a critical role in vascular diseases and host immune response. Recently, our research discovered that LOX-1 could facilitate the uptake of dying cells and cross-presentation of cellular antigen via binding with heat shock proteins, which have a close relationship with gastric neoplasia. Therefore, we speculated that LOX-1 may serve as an oncogene in gastric cancer (GC) development and progression. In this study, through immunohistochemistry staining assay and cancer-related databases, we found that LOX-1 expression was up-regulated in GC tissues and correlated with a poor prognosis in GC patients. The expression of LOX-1 was an independent prognostic factor for OS in GC patients, and the incorporation of LOX-1 with TNM stage is more accurate for predicting prognosis. Additionally, in vitro study by transwell assay and western blot analysis confirmed that LOX-1 could promote the migration and invasion of GC cells by driving epithelial-mesenchymal transition and PI3K/Akt/GSK3β activation. Taken together, we first explored the expression profiles, clinical significance and biological function of LOX-1 in GC, and these data suggest that LOX-1 may represent a promising prognostic biomarker for GC and offer a novel molecular target for GC therapies.