Townson Jason L, Naumov George N, Chambers Ann F
Department of Medical Biophysics, University of Western Ontario, London, Canada N6A 4L6.
Curr Mol Med. 2003 Nov;3(7):631-42. doi: 10.2174/1566524033479483.
Metastasis, the process by which cancer spreads from a primary to a secondary site, is responsible for the majority of cancer related deaths. Yet despite the detrimental effects of metastasis, it is an extremely inefficient process by which very few of the cells that leave the primary tumor give rise to secondary tumors. Metastasis can be considered as a series of sequential steps that begins with a cell leaving a primary tumor, and concludes with the formation of a metastatic tumor in a distant site. During the process of metastasis cells are subjected to various apoptotic stimuli. Thus, in addition to genetic changes that promote unregulated proliferation, successful metastatic cells must have a decreased sensitivity to apoptotic stimuli. As many cancer cells exhibit aberrations in the level and function of key apoptotic regulators, exploiting these alterations to induce tumor cell apoptosis offers a promising therapeutic target. This review will examine the apoptotic regulators that are often aberrantly expressed in metastatic cells; the role that these regulators may play in metastasis; the steps of metastasis and their susceptibility to apoptosis; and finally, current and future cancer prognostics and treatment targets based on apoptotic regulators.
转移是癌症从原发部位扩散到继发部位的过程，它导致了大多数与癌症相关的死亡。然而，尽管转移具有有害影响，但它却是一个效率极低的过程，离开原发肿瘤的细胞中只有极少数会形成继发肿瘤。转移可被视为一系列连续步骤，始于细胞离开原发肿瘤，终于在远处部位形成转移瘤。在转移过程中，细胞会受到各种凋亡刺激。因此，除了促进不受控制增殖的基因变化外，成功的转移细胞对凋亡刺激的敏感性必须降低。由于许多癌细胞在关键凋亡调节因子的水平和功能上表现出异常，利用这些改变来诱导肿瘤细胞凋亡提供了一个有前景的治疗靶点。本综述将探讨在转移细胞中经常异常表达的凋亡调节因子；这些调节因子在转移中可能发挥的作用；转移的步骤及其对凋亡的敏感性；最后，基于凋亡调节因子的当前和未来癌症预后及治疗靶点。
