title: Novel PKC-ζ to p47 phox interaction is necessary for transformation from blebbishields.
abstract: Cancer stem cells are capable of transformation after apoptosis through the blebbishield emergency program. Reactive oxygen species (ROS) play an essential role in transformation. Understanding how ROS are linked to blebbishield-mediated transformation is necessary to develop efficient therapeutics that target the resurrection of cancer stem cells. Here we demonstrate that a novel PKC-ζ to p47(phox) interaction is required for ROS production in cancer cells. The combined use of the S6K inhibitor BI-D1870 with TNF-α inhibited the PKC-ζ to p47(phox) interaction, inhibited ROS production, degraded PKC-ζ, and activated caspases-3 and -8 to block transformation from blebbishields. BI-D1870 also inhibited transformation from cycloheximide-generated blebbishields. Thus ROS and the PKC-ζ to p47(phox) interaction are valid therapeutic targets to block transformation from blebbishields.
authors.affiliation: Department of Urology, Unit 1373, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA.
authors.forename: Goodwin G
authors.initials: GG
authors.lastname: Jinesh
authors.affiliation: Department of Urology, Unit 1373, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA.
authors.forename: Rikiya
authors.initials: R
authors.lastname: Taoka
authors.affiliation: Department of Urology, Unit 1373, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Urology, Unit 1373, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Gorantla
authors.affiliation: Department of Urology, Unit 1373, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA.
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kamat
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D011621:Pteridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000099221:Protein Kinase C zeta
chemical_list: D053148:Caspase 3; D053181:Caspase 8; D003513:Cycloheximide; D019255:NADPH Oxidases; D011493:Protein Kinase C; D011621:Pteridines; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000099221:Protein Kinase C zeta; C516541:BI D1870; C060505:neutrophil cytosolic factor 1; C505407:CASP3 protein, human; C505530:CASP8 protein, human