Blebbishields, the emergency program for cancer stem cells: sphere formation and tumorigenesis after apoptosis
Blebbishields, the emergency program for cancer stem cells: sphere formation and tumorigenesis after apoptosis
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DOI：
10.1038/cdd.2012.140
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发表时间：
2013-03-01
影响因子：
12.4
通讯作者：
Kamat, A. M.
中科院分区：
文献类型：
--
作者：
Jinesh, G. G.;Choi, W.;Kamat, A. M.
半胱天冬酶介导细胞凋亡，也与干细胞生物学有关。半胱天冬酶与干细胞生物学的联系尚不清楚。在这里，我们表明癌细胞的凋亡水泡融合在一起，形成新的结构称为“水泡屏障”。气泡盾通过熔合形成球体。泡盾形成和球体形成均涉及活性半胱天冬酶和N-连接糖基化。球形形成被酸性pH增强，并被质子泵、半胱天冬酶和胆固醇的抑制剂抵消。来自VEGFR 2（高）细胞的滤过泡屏障能够增强球体形成。滤过泡表达瞬时下调的干细胞标志物，形成球形滤过泡的衍生细胞具有致瘤性。我们的研究表明，肿瘤干细胞在凋亡后可以通过形成滤过泡和随后的球体形成而存活。Cell Death and Differentiation（2013）20，382-395; doi：10.1038/cdd.2012.140; 2012年11月23日在线发表
Caspases mediate apoptosis and have also been implicated in stem-cell biology. How caspases are linked to stem-cell biology is not known. Here, we show that the apoptotic blebs of cancer cells fuse together to form novel structures called 'blebbishields'. Blebbishields form spheres by fusion. Both blebbishield formation and sphere formation involve active caspases and N-linked glycosylation. Sphere formation is enhanced by acidic pH and is counteracted by inhibitors of proton pump, caspases, and cholesterol. The blebbishields from VEGFR2(High) cells are capable of enhanced sphere formation. Blebbishields express transiently downregulated stem-cell markers and the sphere-forming blebbishield-derived cells are tumorigenic. Our study demonstrates that the cancer stem cells can survive after apoptosis by blebbishield formation and subsequent sphere formation. Cell Death and Differentiation (2013) 20, 382-395; doi:10.1038/cdd.2012.140; published online 23 November 2012