CD36 mediates palmitate acid-induced metastasis of gastric cancer via AKT/GSK-3/-catenin pathway
CD36 mediates palmitate acid-induced metastasis of gastric cancer via AKT/GSK-3/-catenin pathway
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CD36通过AKT/GSK-3/-catenin通路介导棕榈酸诱导的胃癌转移
DOI：
10.1186/s13046-019-1049-7
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发表时间：
2019-02-04
影响因子：
11.3
通讯作者：
Li, Chen
中科院分区：
文献类型：
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作者：
Pan, Jiaomeng;Fan, Zhiyuan;Li, Chen
背景胃癌（GC）明显倾向于向主要由脂肪组织组成的网膜转移，表明脂肪酸可能导致这种现象。然而，它们在 GC 中的功能仍然知之甚少。本研究探讨棕榈酸(PA)及其细胞受体CD36在GC进展中的作用。方法采用免疫组织化学(IHC)染色法检测GC组织中CD36的表达情况,并统计其临床意义。 CD36过表达和敲低表达细胞模型被开发并在体外进行测试。进行伤口愈合试验、迁移试验和侵袭试验，并将腹膜植入裸鼠体内以评估PA和CD36的生物学效应。采用蛋白质印迹、免疫荧光（IF）、实时定量PCR（qRT-PCR）和抗体封闭实验研究其潜在机制。结果PA通过AKT磷酸化促进GC转移，AKT通过磷酸化灭活GSK-3促进β-catenin的核定位。 PA 的这种促肿瘤作用是由脂肪酸 (FA) 细胞表面受体 CD36 介导的。根据TCGA数据库、GEO数据库和我们自己的临床数据，GC组织中CD36表达水平越高，患者的预后越差。结论我们的实验证实CD36通过AKT/GSK-3/-catenin信号通路作为FA诱导GC转移的关键介质。因此，CD36 可能构成 GC 临床干预的潜在治疗靶点。
BackgroundGastric cancer (GC) has a clear predilection for metastasis toward the omentum which is primarily composed of adipose tissue, indicating that fatty acids may contribute to this phenomenon. However their function remains poorly understood in GC. In this study, we investigated the role of palmitate acid (PA) and its cellular receptor CD36 in the progression of GC.MethodsImmunohistochemical (IHC) staining was performed to detect CD36 expression in GC tissues and its clinical significance was determined statistically. CD36 over-expression and knock-down expression cell models were developed and tested in vitro. Wound-healing assays, migration assays, and invasion assays were performed and peritoneal implants into nude mice were done to assess the biological effects of PA and CD36. The underlying mechanisms were investigated using western blot, immunofluorescence (IF), quantitative real-time PCR (qRT-PCR) and antibody blocking assays.ResultsPA promoted the metastasis of GC by phosphorylation of AKT, which facilitated the nuclear localization of -catenin through inactivation of GSK-3 via phosphorylation. This tumor-promoting effect of PA was mediated by CD36, a cell surface receptor of fatty acids (FAs). The higher the CD36 expression levels in GC tissues correlated with the poorer the prognosis of patients according to the TCGA database, the GEO database and our own clinical data.ConclusionsOur experiments established CD36 as a key mediator of FA-induced metastasis of GC via the AKT/GSK-3/-catenin signaling pathway. CD36 might, therefore, constitute a potential therapeutic target for clinical intervention in GC.