TIEG1 Inhibits Breast Cancer Invasion and Metastasis by Inhibition of Epidermal Growth Factor Receptor (EGFR) Transcription and the EGFR Signaling Pathway
TIEG1 Inhibits Breast Cancer Invasion and Metastasis by Inhibition of Epidermal Growth Factor Receptor (EGFR) Transcription and the EGFR Signaling Pathway
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TIEG1 通过抑制表皮生长因子受体 (EGFR) 转录和 EGFR 信号通路来抑制乳腺癌侵袭和转移
DOI：
10.1128/mcb.06152-11
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发表时间：
2012-01-01
影响因子：
5.3
通讯作者：
Shao, Zhi-ming
中科院分区：
文献类型：
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作者：
Jin, Wei;Chen, Bo-bin;Shao, Zhi-ming
摘要TIEG 1能诱导肿瘤细胞凋亡，但其在抑制肿瘤侵袭和转移中的作用尚未见报道。在这项研究中，我们发现，减少TIEG 1表达与乳腺癌组织和细胞系中人表皮生长因子受体（EGFR）表达增加有关。TIEG 1通过直接结合EGFR启动子在抑制EGFR转录中起重要作用。尽管TIEG 1的过表达减弱EGFR表达，但TIEG 1的敲低刺激EGFR表达。此外，TIEG 1和HDAC 1形成复合物，其结合EGFR启动子上的Sp1位点并通过抑制组蛋白乙酰化来抑制其转录。TIEG 1通过抑制EGFR基因转录和EGFR信号通路，显著抑制乳腺癌细胞侵袭，抑制小鼠异种移植物中的乳腺肿瘤发生，并减少肺转移。因此，TIEG 1是一种抗转移基因产物; TIEG 1对EGFR表达的调节可能是决定和解释乳腺癌侵袭和转移的完整信号通路的一部分。
ABSTRACT TIEG1 can induce apoptosis of cancer cells, but its role in inhibiting invasion and metastasis has not been reported and is unclear. In this study, we find that decreased TIEG1 expression is associated with increased human epidermal growth factor receptor (EGFR) expression in breast cancer tissues and cell lines. TIEG1 plays an important role in suppressing transcription of EGFR by directly binding to the EGFR promoter. While overexpression of TIEG1 attenuates EGFR expression, knockdown of TIEG1 stimulates EGFR expression. Furthermore, TIEG1 and HDAC1 form a complex, which binds to Sp1 sites on the EGFR promoter and inhibits its transcription by suppressing histone acetylation. TIEG1 significantly inhibits breast cancer cell invasion, suppresses mammary tumorigenesis in xenografts in mice, and decreases lung metastasis by inhibition of EGFR gene transcription and the EGFR signaling pathway. Therefore, TIEG1 is an antimetastasis gene product; regulation of EGFR expression by TIEG1 may be part of an integral signaling pathway that determines and explains breast cancer invasion and metastasis.