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

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.

Expansion of breast cancer stem cells with fibrous scaffolds

“…These spheres probably came from multiple cells fusion. 34,35 Those data suggests that CSCs expanded in those mammary cancer cell lines when cultured in electrospun PCL fibrous scaffolds. OCT3/4 and SOX2 function cooperatively to regulate their own transcription and the transcription of a large set of other genes, which control the self-renewal and pluripotency of stem cells.…”

Green Tropical Phytoextracts - Promising Anticancer Alternative

“…The early event of the apoptosis includes the exposure of phosphotidylserine on the cell membrane. The plasma membrane integrity is severely compromised during late apoptotic stages (45,46). The prostate cancer cells under the effect of the tropical plant extracts (in this work) showed the blabbing of outer wall of plasma membrane hinting toward the fact that apoptosis had already kickedoff.…”

Blebbishield emergency program: an apoptotic route to cellular transformation

“…1 We have found that cancer stem cells undergoing apoptosis can avoid cell death by evoking the 'blebbishield emergency program' to enter cellular transformation. 2,3 In the blebbishield emergency program, the first visual sign that indicates the course of apoptosis is being reversed is the construction of blebbishields from apoptotic bodies. 2 Blebbishield construction requires endocytosis and endocytosis-driven serpentine filopodia formation that tether the apoptotic bodies together and facilitate fusion ( Figure 1a).…”

“…2,3 In the blebbishield emergency program, the first visual sign that indicates the course of apoptosis is being reversed is the construction of blebbishields from apoptotic bodies. 2 Blebbishield construction requires endocytosis and endocytosis-driven serpentine filopodia formation that tether the apoptotic bodies together and facilitate fusion ( Figure 1a). 2,3 Inhibition of dynamin-dependent endocytosis blocks the action of serpentine filopodia, inhibits blebbishield formation, and promotes apoptotic body formation.…”

“…2 Blebbishield construction requires endocytosis and endocytosis-driven serpentine filopodia formation that tether the apoptotic bodies together and facilitate fusion ( Figure 1a). 2,3 Inhibition of dynamin-dependent endocytosis blocks the action of serpentine filopodia, inhibits blebbishield formation, and promotes apoptotic body formation. 3 These mechanical steps require energy and functional mitochondria to generate adenosine triphosphate (ATP).…”