title: Mitochondrial oligomers boost glycolysis in cancer stem cells to facilitate blebbishield-mediated transformation after apoptosis.
abstract: Apoptosis culminates in secondary necrosis due to lack of ATP. Cancer stem cells form spheres after apoptosis by evoking the blebbishield emergency program. Hence, determining how blebbishields avoid secondary necrosis is crucial. Here we demonstrate that N-Myc and VEGFR2 control transformation from blebbishields, during which oligomers of K-Ras, p27, BAD, Bax, and Bak boost glycolysis to avoid secondary necrosis. Non-apoptotic cancer cells also utilize oligomers to boost glycolysis, which differentiates the glycolytic function of oligomers from their apoptotic action. Smac mimetic in combination with TNF-α or TRAIL but not in combination with FasL abrogates transformation from blebbishields by inducing secondary necrosis. Thus blebbishield-mediated transformation is dependent on glycolysis, and Smac mimetics represent potential candidates to abrogate the blebbishield emergency program.
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: G G
authors.initials: GG
authors.lastname: Jinesh
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Molina
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.affiliation: Astra Zeneca , Boston, MA, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Laing
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: G B
authors.initials: GB
authors.lastname: Mills
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bar-Eli
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Kamat