Topic
Blebbishield emergency program
About: Blebbishield emergency program is a research topic. Over the lifetime, 8 publications have been published within this topic receiving 173 citations.
Papers
TL;DR: This review tracks the genetic aspects of K-Ras signaling networks and assembles the sequence of cellular events that constitute the tumorigenesis process, such as regulation ofkirsten-rat sarcoma viral oncogene homolog, generation of reactive oxygen species (ROS), induction ofDNA damage and apoptosis, induction of DNA damage repair pathways and ROS detoxification systems.
Abstract: Cellular transformation and the accumulation of genomic instability are the two key events required for tumorigenesis. K-Ras (Kirsten-rat sarcoma viral oncogene homolog) is a prominent oncogene that has been proven to drive tumorigenesis. K-Ras also modulates numerous genetic regulatory mechanisms and forms a large tumorigenesis network. In this review, we track the genetic aspects of K-Ras signaling networks and assemble the sequence of cellular events that constitute the tumorigenesis process, such as regulation of K-Ras expression (which is influenced by miRNA, small nucleolar RNA and lncRNA), activation of K-Ras (mutations), generation of reactive oxygen species (ROS), induction of DNA damage and apoptosis, induction of DNA damage repair pathways and ROS detoxification systems, cellular transformation after apoptosis by the blebbishield emergency program and the accumulation of genomic/chromosomal instability that leads to tumorigenesis.
89 citations
TL;DR: It is demonstrated that dimers and trimers of p19-VHL interact with RalBP1 to construct blebbishields and play an oncogenic role, whereas p30-V HL plays a tumor suppressor role during the bleBBishield emergency program by regulating oxidative stress management genes.
Abstract: Cancer stem cells evade apoptotic death by blebbishield emergency program, which constructs blebbishields from apoptotic bodies and drives cellular transformation Von Hippel-Lindau (VHL) plays both tumor suppressor and oncogenic roles, and the reason behind is poorly understood Here we demonstrate that dimers and trimers of p19-VHL interact with RalBP1 to construct blebbishields Expression of RalBP1, p19-VHL, and high-molecular weight VHL is required to evade apoptosis by blebbishield-mediated transformation In contrast, p30-VHL plays a tumor suppressor role by inhibiting blebbishield-mediated transformation Furthermore, target genes of VHL that suppress oxidative stress were elevated during blebbishield-mediated cellular transformation Thus, RalBP1 and p19-VHL play an oncogenic role, whereas p30-VHL plays a tumor suppressor role during the blebbishield emergency program by regulating oxidative stress management genes
19 citations
TL;DR: It is demonstrated that CF3DODA-Me induced apoptosis, degraded Sp1, inhibited the expression of multiple drivers of the blebbishield emergency program such as VEGFR2, p70S6K, and N-Myc through activation of caspase-3, inhibited reactive oxygen species; and inhibited K-Ras activation to abolish transformation from bleBBishields as well as transformation in soft agar.
Abstract: Cancer stem cells are capable of undergoing cellular transformation after commencement of apoptosis through the blebbishield emergency program in a VEGF-VEGFR2-dependent manner. Development of therapeutics targeting the blebbishield emergency program would thus be important in cancer therapy. Specificity protein 1 (Sp1) orchestrates the transcription of both VEGF and VEGFR2; hence, Sp1 could act as a therapeutic target. Here, we demonstrate that CF3DODA-Me induced apoptosis, degraded Sp1, inhibited the expression of multiple drivers of the blebbishield emergency program such as VEGFR2, p70S6K, and N-Myc through activation of caspase-3, inhibited reactive oxygen species; and inhibited K-Ras activation to abolish transformation from blebbishields as well as transformation in soft agar. These findings confirm CF3DODA-Me as a potential therapeutic candidate that can induce apoptosis and block transformation from blebbishields.
19 citations
TL;DR: It is demonstrated that the blebbishield emergency program drives evasion of chromosomal instability and phagocytosis checkpoints by apoptotic cancer stem cells.
Abstract: Genomic instability and immune evasion are hallmarks of cancer. Apoptotic cancer stem cells can evade cell death by undergoing cellular transformation by constructing "blebbishields" from apoptotic bodies. In this study, we report a novel linkage between genomic instability and phagocytosis evasion that is coordinated by the blebbishield emergency program. Blebbishield emergency program evaded genomic instability checkpoint, expressed genomic instability-associated genes at distinct phases of cellular transformation, exhibited chromosomal instability, and promoted increase in nuclear size. Blebbishields fused with immune cells to evade phagocytosis, and the resultant hybrid cells exhibited increased migration, tumorigenesis, metastasis, red blood cell recruitment to tumors, and induced hepatosplenomegaly with signatures of genomic instability, blebbishield emergency program, and phagocytosis evasion to offer poor prognosis. Overall, our data demonstrate that the blebbishield emergency program drives evasion of chromosomal instability and phagocytosis checkpoints by apoptotic cancer stem cells. Cancer Res; 77(22); 6144-56. ©2017 AACR.
TL;DR: ROS and the PKC-ζ to p47phox interaction are valid therapeutic targets to block 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.
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2018 | 1 |
| 2017 | 3 |
| 2016 | 4 |