Journal
CELL DEATH AND DIFFERENTIATION
Volume 20, Issue 3, Pages 382-395Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2012.140
Keywords
apoptosis; blebbishields; cancer stem cells; VEGFR2; p70S6K; caspase
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Funding
- MD Anderson Cancer Center
- Clayton Foundation for Research
- National Institutes of Health through MD Anderson Cancer Center's Support Grant [CA016672]
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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
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