肿瘤细胞间相互作用:Notch-1信号转导与调控机制
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国家自然科学基金项目 (11272083, 31470906, 11502049),四川省杰出青年基金项目(2014JQ0008)


Cancer cell-cell interaction: Notch-1 signaling pathway and its regulation mechanisms
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    摘要:

    Notch-1信号通路在细胞分化、发育以及增殖、凋亡方面起重要作用,并参与肿瘤的发生发展,与肿瘤的侵袭、运动和转移过程密切相关。活化的Notch-1信号通路能够直接或间接调控细胞的增殖和迁移,促进肿瘤细胞发生上皮细胞间充质转换,并维持其间充质特性,增强肿瘤细胞的黏附能力。同时,Notch信号通路与PI3K/Akt、NF-κB等途径交互作用,将信号级联放大,从而加强调控肿瘤细胞的恶性行为。多种实体瘤中存在异常活化的Notch-1信号通路。从Notch的结构和功能、Notch-1信号通路与肿瘤发生和转移的关系、Notch-1调控肿瘤转移的分子机制与调控网络和以Notch为靶点的肿瘤治疗5个方面进行综述。阐明Notch-1信号通路在肿瘤转移过程中的作用与调控机制以及目前针对Notch-1信号通路的治疗策略,能够为肿瘤的病理机制和临床治疗研究提供参考信息。

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    Notch-1 signaling pathway is responsible for cell differentiation, development, proliferation and apoptosis. Recent studies show that Notch-1 signaling pathway is also involved in cancer progression, including cell invasion, motility and cancer metastasis. Activation of Notch-1 signaling pathway can directly or indirectly induce cell proliferation and migration. In tumor cells, activation of Notch-1 facilitates epithelial-mesenchymal transition (EMT), keeps its mesenchyme characteristics and induces cell adhesion. Notch-1 signaling pathway also cross-talks with other pathways to regulate cell fate, such as PI3K/Akt, NF-κB pathways. The evidence shows that aberrant Notch-1 activation has been found in different solid tumors, which participates in regulating tumor metastasis. In this review, the Notch structure and function, Notch-1 signal and tumorigenesis, tumor metastasis via Notch-1 signaling, and Notch-1 signaling targeted-therapy were comprehensively summarized. To clarify the roles of Notch-1 signal pathway in tumor metastasis and its regulatory mechanisms as well as the current treatment strategies for Notch-1 signal pathway will provide references for studies on pathomechanism and clinical treatment of cancers.

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李莉,熊妮娅,张婧,杨红,吴春惠,刘贻尧.肿瘤细胞间相互作用:Notch-1信号转导与调控机制[J].医用生物力学,2016,31(3):284-290

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  • 收稿日期:2015-11-08
  • 最后修改日期:2015-12-15
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  • 在线发布日期: 2016-06-29
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