Figure 1.

Cell biology and therapeutic targets of the blebbishield emergency program. (a) Cell biological events of the blebbishield emergency program. Endocytosis inhibition blocks blebbishield formation and promote apoptotic body formation, whereas neutralizing antibodies to VEGF or VEGFR2 blocks transformation from blebbishields. (b) Differential regulation of glycolysis and secondary necrosis by Smac mimetic (AZ58) in combination with TNF-α, TRAIL, and FasL determines the fate of apoptotic cancer stem cells. Inhibition of IRES translation is critical to block transformation from blebbishields. Note: oligomers depicted could be homo-oligomers and/or hetero-oligomers in nature. (c) Caspase-3 blocks p70S6K and Pim-1 yet required for transformation as z-DEVD-fmk blocks transformation. (d) The blebbishield emergency program is an essential intermediate step in K-Ras-induced transformation as both K-Ras and blebbishields utilize p27, Pim-1, N-Myc and BAD-mediated glycolytic switch for transformation