TIP30 nuclear translocation negatively regulates EGF-dependent cyclin D1 transcription in human lung adenocarcinoma
TIP30 nuclear translocation negatively regulates EGF-dependent cyclin D1 transcription in human lung adenocarcinoma
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TIP30核易位负向调节人肺腺癌中EGF依赖性细胞周期蛋白D1转录
DOI：
10.1016/j.canlet.2014.08.008
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发表时间：
2014
期刊：
影响因子：
9.7
通讯作者：
Li Aimin
中科院分区：
文献类型：
--
作者：
Shuai Shuai;Yan Xiao;Zhang Junyi;Kang Shijun;Chen Fengsheng;Luo Rongcheng;Li Aimin
异常的表皮生长因子（EGF）依赖性信号在人类肿瘤的进展中起着关键作用。我们发现，TIP30，一种肿瘤抑制蛋白，在EGF处理后，易位到人肺腺癌细胞的细胞核中，EGFR信号通路的选择性抑制剂阻断了这种作用。染色质免疫沉淀分析显示，TIP30通过HDAC1依赖性机制负调控EGF依赖性CCND1转录激活。在肺腺癌患者中，核TIP30的水平与EGFR和cyclin D1的水平呈负相关。这些发现表明，核TIP30诱导的细胞周期蛋白D1转录下调拮抗EGFR信号转导和抑制肿瘤发生。
Aberrant epidermal growth factor (EGF)-dependent signaling plays a key role in the progression of human carcinomas. We found that TIP30, a tumor suppressor protein, translocated into the nucleus of human lung adenocarcinoma cells following EGF treatment, and the selective inhibitors of EGFR signaling pathways blocked this effect. Chromatin immunoprecipitation assays revealed that TIP30 negatively regulated EGF-dependent transcriptional activation of CCND1 through a HDAC1-dependent mechanism. In lung adenocarcinoma patients, the level of nuclear TIP30 was inversely correlated with that of EGFR and cyclin D1. These findings suggest that nuclear TIP30-induced downregulation of cyclin D1 transcription antagonizes EGFR signaling and suppresses tumorigenesis.