组蛋白乙酰化修饰H4K16ac参与乳腺癌Notch1信号传导

Ya-qi Wang, Jinghao Zhang, Zhao-yuan Wan, D. Li
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引用次数: 0

摘要

Notch信号通路是一个基本的细胞间信号系统,在多种组织中调节细胞增殖和分化的命运决定。Notch1信号通路异常激活可导致多种疾病,包括恶性肿瘤。Notch受体活性失调与乳腺癌有关,但其表观遗传机制尚不清楚。与癌旁组织相比,癌组织中NIC1高表达,H4K16ac低表达。Notch1在乳腺癌细胞系MCF-7中被敲低,导致H4K16ac表达增加,同时导致其增殖和迁移能力降低。我们的研究提示H4K16ac参与Notch1在乳腺癌细胞中的信号转导。这些结果证实了Notch1在乳腺癌细胞中是一个触发表观遗传机制的信号,可能与肿瘤的传播、转移和增殖有关。因此,确定与NOTCH信号相互作用的特定因子可能与充分了解NOTCH在乳腺肿瘤中的作用有关。
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Histone Acetylation Modification H4K16ac Involved in Notch1 Signaling in Breast Cancer
The Notch signaling pathway is a fundamental intercellular signaling system that regulates cell fate decisions in terms of proliferation and differentiation in multiple tissues. Abnormal activation of Notch1 signaling pathway leads to a variety of diseases, including the malignant tumors. Dysregulated Notch receptor activity has been implicated in breast cancer but the epigenetic mechanisms remains not clear. Compared to adjacent tissues, high expression of NIC1 and low expression of H4K16ac were found in cancer tissues. Notch1 knocked down in the breast cancer cell line MCF-7 resulted in increased H4K16ac expression and a parallel reduction in their proliferation and migration capacity. Our study prompting H4K16ac to participate in the signal transduction of Notch1 in breast cancer cells. These results confirm Notch1 as a signal triggering epigenetic mechanisms in breast cancer cells, which may have implications in tumor dissemination, metastasis and proliferation. The identification of specific factors interacting with NOTCH signaling could thus be relevant to fully understanding the role of NOTCH in breast neoplasia.
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