Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China.
Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang 110001, China.
Aging (Albany NY). 2020 Nov 21;13(2):1883-1897. doi: 10.18632/aging.103985.
Evidence indicates that the lipid scavenger receptor CD36 has pro-metastatic functions in several cancers. Although CD36 expression correlates with an unfavorable prognosis in gastric cancer (GC), its specific contribution to disease onset, progression, and/or metastasis remains unclear. Using bioinformatics analyses, we ascertained that CD36 expression was increased in metastatic GC specimens in The Cancer Genome Atlas and Gene Expression Omnibus databases and correlated with poor prognosis. In addition, higher CD36 expression was associated with lymph node metastasis ( < 0.05) and poor prognosis ( = 0.030) in 79 Chinese GC patients. Basal CD36 expression levels correlated positively with migration, invasion, and expression of epithelial-to-mesenchymal transition (EMT) markers in GC cell lines, a relationship confirmed by knockdown and overexpression experiments. Importantly, analysis of gene expression changes in CD36-knockdown GC cells led us to identify the chromatin-associated protein DEK as a c-Myc target that mediates activation of the GSK-3β/β-catenin signaling pathway to trigger EMT. These findings further our understanding of the mechanisms governing metastatic dissemination of GC cells and suggest the therapeutic potential of strategies targeting CD36.
证据表明，脂质清道夫受体 CD36 在几种癌症中具有促转移功能。虽然 CD36 的表达与胃癌（GC）的预后不良相关，但它对疾病发生、进展和/或转移的具体贡献仍不清楚。通过生物信息学分析，我们确定了 CD36 的表达在癌症基因组图谱和基因表达综合数据库中的转移性 GC 标本中增加，并与不良预后相关。此外，在 79 例中国 GC 患者中，较高的 CD36 表达与淋巴结转移（<0.05）和不良预后（=0.030）相关。GC 细胞系中，CD36 的基础表达水平与迁移、侵袭和上皮-间充质转化（EMT）标志物的表达呈正相关，这一关系通过敲低和过表达实验得到了证实。重要的是，对 CD36 敲低 GC 细胞中基因表达变化的分析使我们发现了染色质相关蛋白 DEK 是 c-Myc 靶向的，它介导 GSK-3β/β-catenin 信号通路的激活，从而触发 EMT。这些发现进一步加深了我们对控制 GC 细胞转移扩散机制的理解，并表明靶向 CD36 的治疗策略具有潜在的治疗效果。
