GATA1 induces epithelial-mesenchymal transition in breast cancer cells through PAK5 oncogenic signaling.
GATA1 induces epithelial-mesenchymal transition in breast cancer cells through PAK5 oncogenic signaling.
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GATA1 通过 PAK5 致癌信号诱导乳腺癌细胞上皮间质转化
DOI：
10.18632/oncotarget.2999
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发表时间：
2015-02-28
期刊：
影响因子：
--
通讯作者：
Li F
中科院分区：
文献类型：
--
作者：
Li Y;Ke Q;Shao Y;Zhu G;Li Y;Geng N;Jin F;Li F
上皮-间充质转化(EMT)是肿瘤转移级联过程中的一个关键过程，其特征是细胞-细胞连接的丢失，导致获得迁移和侵袭特性。E-钙粘附素是细胞间连接的主要成分，其表达的降低或缺失是EMT的一个标志。转录因子GATA1在乳腺癌中具有重要的抗凋亡作用，但其在转移中的作用尚未被研究。在这里，我们发现GATA1作为一种新的E-钙粘素抑制物，促进了乳腺癌细胞的EMT。GATA1与E-钙粘蛋白启动子结合，下调E-钙粘蛋白的表达，破坏细胞间连接，促进乳腺癌细胞体内转移。此外，GATA1是p21激活的蛋白5(PAK5)的新底物，PAK5在丝氨酸161和187(S161和S187)上被磷酸化。GATA1将HDAC3/4招募到E-钙粘蛋白启动子，该启动子被GATA1 S161AS187A突变体还原。这些数据表明，磷酸化的GATA1招募了更多的HDAC3/4来促进E-钙粘蛋白的转录抑制，导致乳腺癌细胞的EMT。我们的发现为GATA1的新功能提供了洞察力，有助于更好地理解EMT，表明GATA1及其磷酸化可能在乳腺癌的转移中发挥重要作用。
Epithelial-mesenchymal transition (EMT) is a key process in tumor metastatic cascade that is characterized by the loss of cell-cell junctions, resulting in the acquisition of migratory and invasive properties. E-cadherin is a major component of intercellular junctions and the reduction or loss of its expression is a hallmark of EMT. Transcription factor GATA1 has a critical anti-apoptotic role in breast cancer, but its function for metastasis has not been investigated. Here, we found that GATA1, as a novel E-cadherin repressor, promotes EMT in breast cancer cells. GATA1 binds to E-cadherin promoter, down-regulates E-cadherin expression, disrupts intercellular junction and promotes metastasis of breast cancer cell in vivo. Moreover, GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells. Our findings provide insights into the novel function of GATA1, contributing to a better understanding of the EMT, indicating that GATA1 and its phosphorylation may play an important role in the metastasis of breast cancer.
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DOI：
10.1016/j.biocel.2005.06.017
发表时间：
2006-01-01
影响因子：
4
作者：
Lowry, JA;Mackay, JP
通讯作者：
Mackay, JP
组蛋白脱乙酰化参与 MORC2 介导的碳酸酐酶 IX 下调
影响因子：
14.9
作者：
Shao Y;Li Y;Zhang J;Liu D;Liu F;Zhao Y;Shen T;Li F
通讯作者：
Li F
PAK5-Egr1-MMP2信号控制乳腺癌细胞的迁移和侵袭
影响因子：
--
作者：
Wang, Xiao-Xia;Cheng, Qian;Zheng, Jun-Nian
通讯作者：
Zheng, Jun-Nian
影响因子：
3.1
作者：
Whale, Andrew;Hashim, Fariesha Nur;Wells, Claire M.
通讯作者：
Wells, Claire M.
影响因子：
2.5
作者：
Hardy, Katharine M.;Booth, Brian W.;Hendrix, Mary J. C.;Salomon, David S.;Strizzi, Luigi
通讯作者：
Strizzi, Luigi