Inhibitor of Differentiation/DNA Binding 1 (ID1) Inhibits Etoposide-induced Apoptosis in a c-Jun/c-Fos-dependent Manner
Inhibitor of Differentiation/DNA Binding 1 (ID1) Inhibits Etoposide-induced Apoptosis in a c-Jun/c-Fos-dependent Manner
复制标题
分化/DNA 结合抑制剂 1 (ID1) 以 c-Jun/c-Fos 依赖性方式抑制依托泊苷诱导的细胞凋亡
DOI：
10.1074/jbc.m115.704361
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发表时间：
2016-03-25
影响因子：
4.8
通讯作者：
Liu, Zhihua
中科院分区：
文献类型：
--
作者：
Zhao, Yahui;Luo, Aiping;Liu, Zhihua
ID 1（inhibitor of differentiation/DNA binding 1，分化抑制剂/DNA结合抑制剂1）在转移、肿瘤发生和维持细胞活力中起重要作用。研究表明，ID 1的上调与人类癌症的不良预后和对化疗的耐药性相关。然而，潜在的分子机制仍然难以捉摸。在这里，我们首次确定了依托泊苷激活后上调ID 1是通过ID 1启动子内的AP-1结合位点介导的，并证实了ID 1增强了食管鳞状细胞癌细胞对DNA损伤诱导的凋亡的细胞抵抗力。c-Jun/c-Fos或ID 1表达的消除通过增加caspase 3和PARP裂解的活性增强依托泊苷介导的凋亡。此外，c-Jun/c-Fos和ID 1在人类癌症中呈正相关。更重要的是，ID 1和c-Jun或c-Fos的同时高表达与癌症患者的生存率低相关。总的来说，我们证明了c-Jun/c-Fos-ID 1信号通路在食管癌细胞化疗耐药中的重要性，并为理解食管鳞状细胞癌细胞生物学的潜在分子机制提供了相当多的见解。
ID1 (inhibitor of differentiation/DNA binding 1) acts an important role in metastasis, tumorigenesis, and maintenance of cell viability. It has been shown that the up-regulation of ID1 is correlated with poor prognosis and the resistance to chemotherapy of human cancers. However, the underlying molecular mechanism remains elusive. Here, we determined for the first time that up-regulating ID1 upon etoposide activation was mediated through AP-1 binding sites within the ID1 promoter and confirmed that ID1 enhanced cell resistance to DNA damage-induced apoptosis in esophageal squamous cell carcinoma cells. Ablation of c-Jun/c-Fos or ID1 expression enhanced etoposide-mediated apoptosis through increasing activity of caspase 3 and PARP cleavage. Moreover, c-Jun/c-Fos and ID1 were positively correlated in human cancers. More importantly, simultaneous high expression of ID1 and c-Jun or c-Fos was correlated with poor survival in cancer patients. Collectively, we demonstrate the importance of c-Jun/c-Fos-ID1 signaling pathway in chemoresistance of esophageal cancer cells and provide considerable insight into understanding the underlying molecular mechanisms in esophageal squamous cell carcinoma cell biology.