Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, China.
Adv Exp Med Biol. 2012;727:186-98. doi: 10.1007/978-1-4614-0899-4_14.
Cancer metastasis is the leading cause of cancer-related deaths all over the world at present. Accumulated researches have demonstrated that cancer metastasis is composed of a series of successive incidents, mainly including epithelial-mesenchymal transition (EMT), malignant cell migration, resistance to anoikis, and angiogenesis and lymphangiogenesis processes. However, the complicated cellular and molecular mechanisms underlying and modulating these processes have not been well elucidated. Thus, studies on cancer metastasis mechanism may propose possibilities to therapeutically interfere with signaling pathways required for each step of cancer metastasis, therefore inhibiting the outgrowth of distant metastasis of tumors. Recent insights have linked the Notch signaling pathway, a critical pathways governing embryonic development and maintaining tumor stemness, to cancer metastasis. This chapter highlights the current evidence for aberration of the Notch signaling in metastasis of tumors such as osteosarcoma, breast cancer, prostate cancer, and melanoma. In these studies, Notch activity seems to participate in cancer metastasis by modulating the EMT, tumor angiogenesis processes, and the anoikis-resistance of tumor cells. Therefore, manipulating Notch signaling may represent a promising alternative/ complement therapeutic strategy targeting cancer metastasis besides cancer stemness.
癌症转移是目前全世界癌症相关死亡的主要原因。大量研究表明，癌症转移由一系列连续事件组成，主要包括上皮-间充质转化（EMT）、恶性细胞迁移、抗失巢凋亡以及血管生成和淋巴管生成过程。然而，这些过程背后和调节这些过程的复杂细胞和分子机制尚未得到很好的阐明。因此，对癌症转移机制的研究可能为治疗性干预癌症转移的每个步骤所需的信号通路提供可能性，从而抑制肿瘤远处转移的生长。最近的研究结果表明，Notch 信号通路与肿瘤转移有关，Notch 信号通路是一个关键的信号通路，它控制着胚胎发育和维持肿瘤干细胞特性。本章重点介绍 Notch 信号通路在骨肉瘤、乳腺癌、前列腺癌和黑色素瘤等肿瘤转移中的异常情况。在这些研究中，Notch 活性似乎通过调节 EMT、肿瘤血管生成过程以及肿瘤细胞的抗失巢凋亡来参与癌症转移。因此，操纵 Notch 信号通路可能代表一种有前途的替代/补充治疗策略，除了针对癌症干细胞外，还可以针对癌症转移。
