CD36 upregulates DEK transcription and promotes cell migration and invasion via GSK-3β/β-catenin-mediated epithelial-to-mesenchymal transition in gastric cancer.

CD36 upregulates DEK transcription and promotes cell migration and invasion via GSK-3β/β-catenin-mediated epithelial-to-mesenchymal transition in gastric cancer.
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CD36 通过 GSK-3β/β-catenin 介导的胃癌上皮间质转化上调 DEK 转录并促进细胞迁移和侵袭

DOI:
10.18632/aging.103985
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发表时间:
2020-11-21
期刊:
Aging
影响因子:
--
通讯作者:
Liu Y
Liu Y
中科院分区:
其他
文献类型:
--
作者:
Wang J;Wen T;Li Z;Che X;Gong L;Jiao Z;Qu X;Liu Y

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有证据表明,脂质清除剂受体CD36在几种癌症中具有促转移功能。虽然CD36的表达与胃癌的不良预后有关,但其在疾病发生、发展和/或转移中的具体作用尚不清楚。通过生物信息学分析,我们在癌症基因组图谱和基因表达总集数据库中证实了CD36在转移性胃癌组织中的表达增加,并与不良预后相关。此外,在79例中国胃癌患者中,CD36的高表达与淋巴结转移和预后不良有关(p=0.030)。CD36的基础表达水平与GC细胞系的迁移、侵袭和上皮向间充质转化(EMT)标志物的表达呈正相关,基因敲除和过表达实验证实了这种关系。重要的是,对CD36基因敲除的GC细胞中基因表达变化的分析使我们确定染色质相关蛋白DEK是c-Myc的靶点,它介导了GSK-3β/β-catenin信号通路的激活,从而触发了内皮细胞转化。这些发现进一步加深了我们对GC细胞转移扩散机制的理解,并提示了针对CD36的策略的治疗潜力。
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 (p < 0.05) and poor prognosis (p = 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.
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