内质网共伴侣蛋白 ERdj3/DNAJB11 通过抑制 AATZ 的降解促进肝癌的进展。
The endoplasmic reticulum co-chaperone ERdj3/DNAJB11 promotes hepatocellular carcinoma progression through suppressing AATZ degradation.
机构信息
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.
出版信息
Future Oncol. 2018 Dec;14(29):3001-3013. doi: 10.2217/fon-2018-0401. Epub 2018 Jul 11.
AIM
The co-chaperone ERdj3/DNAJB11 is involved in the endoplasmic reticulum stress response observed in cancer cells. We hypothesized that ERdj3 functions as a hepatocellular carcinoma (HCC) oncogene by inhibiting AATZ degradation.
MATERIALS & METHODS: ERdj3 and AATZ expressions were analyzed in 84 HCC patients. Cell proliferation, epithelial-mesenchymal transition marker expression, migration and invasiveness were assessed in HepG2 and Huh-7 cells. A murine xenograft tumor model was constructed.
RESULTS
ERdj3 is upregulated in HCC tumors and cell lines. Tumor ERdj3 levels are positively associated with cirrhosis, enhanced HCC status, inferior survival outcomes and AATZ levels. ERdj3 suppresses AATZ degradation. ERdj3 overexpression enhances proliferation, epithelial-mesenchymal transition marker expression, migration, invasiveness and xenograft tumor growth in an AATZ-dependent manner.
CONCLUSION
ERdj3 enhances HCC progression through suppressing AATZ degradation.
目的
内质网伴侣蛋白 ERdj3/DNAJB11 参与癌细胞内质网应激反应。我们假设 ERdj3 通过抑制 AATZ 降解而发挥肝癌 (HCC) 癌基因的作用。
材料与方法
分析了 84 例 HCC 患者中 ERdj3 和 AATZ 的表达。在 HepG2 和 Huh-7 细胞中评估细胞增殖、上皮-间充质转化标志物表达、迁移和侵袭能力。构建了小鼠异种移植肿瘤模型。
结果
ERdj3 在 HCC 肿瘤和细胞系中上调。肿瘤 ERdj3 水平与肝硬化、增强的 HCC 状态、较差的生存结果和 AATZ 水平呈正相关。ERdj3 抑制 AATZ 降解。ERdj3 过表达以 AATZ 依赖的方式增强增殖、上皮-间充质转化标志物表达、迁移、侵袭和异种移植肿瘤生长。
结论
ERdj3 通过抑制 AATZ 降解增强 HCC 进展。
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