Fe65 Suppresses Breast Cancer Cell Migration and Invasion through Tip60 Mediated Cortactin Acetylation.

Fe65 Suppresses Breast Cancer Cell Migration and Invasion through Tip60 Mediated Cortactin Acetylation.
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DOI:
10.1038/srep11529
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发表时间:
2015-07-13
期刊:
影响因子:
4.6
通讯作者:
Bai W
Bai W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sun Y;Sun J;Lungchukiet P;Quarni W;Yang S;Zhang X;Bai W

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Fe 65是一种脑富集的衔接蛋白,已知其在神经元细胞和阿尔茨海默病中Aβ淀粉样前体蛋白的作用,但对其在癌细胞中的功能知之甚少。本研究首次证明了Fe65在抑制乳腺癌细胞迁移和侵袭中的作用。机制研究表明,抑制是通过其磷酸酪氨酸结合结构域1介导的,该结构域1介导Tip60募集到coronin以刺激其乙酰化。这些研究将Tip60乙酰转移酶确定为转移性乳腺癌治疗干预的细胞质药物靶标。
Fe65 is a brain-enriched adaptor protein known for its role in the action of the Aβ amyloid precursor protein in neuronal cells and Alzheimer’s disease, but little is known about its functions in cancer cells. The present study documents for the first time a role of Fe65 in suppressing breast cancer cell migration and invasion. Mechanistic studies suggest that the suppression is mediated through its phosphotyrosine binding domain 1 that mediates the recruitment of Tip60 to cortactin to stimulate its acetylation. The studies identify the Tip60 acetyltransferase as a cytoplasmic drug target for the therapeutic intervention of metastatic breast cancers.
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