Blebbishields, the emergency program for cancer stem cells: sphere formation and tumorigenesis after apoptosis

被引：54

作者：

Jinesh, G. G. ^{[1
]}

Choi, W. ^{[1
]}

Shah, J. B. ^{[1
]}

Lee, E. K. ^{[1
]}

Willis, D. L. ^{[1
]}

Kamat, A. M. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA

来源：

CELL DEATH AND DIFFERENTIATION | 2013年 / 20卷 / 03期

基金：

美国国家卫生研究院;

关键词：

apoptosis; blebbishields; cancer stem cells; VEGFR2; p70S6K; caspase; EMBRYONIC STEM; GRANZYME-B; TUMOR; VEGF; INHIBITOR; GROWTH; MYC; HETEROGENEITY; ACTIVATION; SURVIVAL;

D O I：

10.1038/cdd.2012.140

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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

引用

页码：382 / 395

页数：14

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