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

G. G. Jinesh, W. Choi, J. B. Shah, E. K. Lee, D. L. Willis, A. M. Kamat

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)382-395
Number of pages14
JournalCell death and differentiation
Volume20
Issue number3
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • VEGFR2
  • apoptosis
  • blebbishields
  • cancer stem cells
  • caspase
  • p70S6K

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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