失巢凋亡及其在肿瘤侵袭转移中的调控Theregulationof-生物通.PDF

HEREDITAS (Beijing) 2012 年*月, 34(*): ISSN 0253-9772 失巢凋亡及其在肿瘤侵袭、转移中的调控 苏红，司晓宇，唐文如，罗瑛 昆明理工大学医学院，衰老与肿瘤分子遗传学实验室，昆明 650500 摘要：作为肿瘤转移的屏障，细胞与邻近细胞或者细胞外基质 （Extracellular matrix ，ECM ）失去联系后将 遭受凋亡，这种细胞死亡方式称为“失巢凋亡” 。正常上皮细胞或不具备转移性质的实体瘤细胞从原位脱落 进入血液循环后就会引发失巢凋亡，失巢凋亡的意义在于防止这些脱落的细胞种植并生长于其他不适宜的 地方。而肿瘤细胞，尤其是一些容易发生远距离转移的恶性肿瘤细胞，具有极强的抗失巢凋亡特性，便于 转移侵袭。研究发现肿瘤细胞能通过多种方式抵抗失巢凋亡，比如细胞自分泌生长因子或者由邻近细胞旁 分泌，激活促存活信号通路；细胞改变整合蛋白的表达模式，使之能够接收新环境的生存信号；活性氧 （Reactive oxygen species，ROS ）通过不依赖配体的方式激活生长因子受体，从而逃逸凋亡；上皮间质转 化 （Epithelial-mesenchymal transition ，EMT ）激活等。这些方式导致细胞存活信号激活和凋亡途径抑制， 最终使肿瘤细胞抗失巢凋亡，促进转移。文章综述了当前研究的肿瘤转移的关键机制，这些策略也将成为 肿瘤治疗的重要靶点。 关键词：失巢凋亡；抗失巢凋亡；转移；存活信号 The regulation of anoikis in tumor invasion and metastasis SU Hong, SI Xiao-Yu, TANG Wen-Ru, LUO Ying Lab of Molecular Genetics of Aging and Tumor, Faculty of Medicine, Kunming University of Science and Technology, Kunming 650500,China Abstract: As a barrier to metastasis of cancer, cells that lost contact with the neighbouring cells or extracellular matrix （Extracellular matrix ，ECM ） will be subjected to apoptosis. This cell death process has been termed “anoikis”. When normal epithelial cells or solid tumor cells without metastatic potential detach from the primary site, and then enter into the circulatory system, the anoikis mechanism will be activated. The significance of anoikis is to prevent the shedding cells from growing and implanting into other inappropriate sites. Tumor cells, especially several malignant cells that is prone to transfer to distant sites, have properties of anti-anoikis, which facilitates metastasis as well as invasion of tumor cells. The studies found that tumor cells can resist anoikis through multiple mechanisms: the pro-survival pathways are activated by cells autocrine growth factors and 收稿日期：2012-04-16； 修回日期：2012-07-12 基金项目：遗传资源与进化国家重点实验室开放课题（编号：GREKF10-07 ），国家自然