Sun Yuefeng, Sun Jianwei, Lungchukiet Panida, Quarni Waise, Yang Shengyu, Zhang Xiaohong, Bai Wenlong
Departments of Pathology and Cell Biology, University of South Florida Morsani College of Medicine, Tampa, FL 33612.
Comprehensive Melanoma Research Center and Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612.
Sci Rep. 2015 Jul 13;5:11529. doi: 10.1038/srep11529.
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.
Fe65是一种在大脑中高度富集的衔接蛋白，因其在神经元细胞中参与β淀粉样前体蛋白的作用以及与阿尔茨海默病相关而闻名，但人们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方面的作用。机制研究表明，这种抑制作用是通过其磷酸酪氨酸结合结构域1介导的，该结构域介导Tip60招募至皮层肌动蛋白以刺激其乙酰化。这些研究确定Tip60乙酰转移酶为转移性乳腺癌治疗干预的细胞质药物靶点。
