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Dysregulation of YAP by ARF Stimulated with Tea-derived Carbon Nanodots
- Source :
- Scientific Reports, Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group UK, 2017.
-
Abstract
- YAP is a downstream nuclear transcription factor of Hippo pathway which plays an essential role in development, cell growth, organ size and homeostasis. It was previously identified that elevation of YAP in genomics of genetic engineered mouse (GEM) model of prostate cancer is associated with Pten/Trp53 inactivation and ARF elevation hypothesizing the essential crosstalk of AKT/mTOR/YAP with ARF in prostate cancer. However, the detailed function and trafficking of YAP in cancer cells remains unclear. Using GEM microarray model, we found ARF dysregulates Hippo and Wnt pathways. In particular, ARF knockdown reduced non-nuclear localization of YAP which led to an increase in F-actin. Mechanistically, ARF knockdown suppressed protein turnover of β-catenin/YAP, and therefore enhanced the activity of AKT and phosphorylation of YAP. Moreover, we found tea-derived carbon dots can interact with ARF in nucleus that may further lead to the non-nuclear localization of YAP. Thus, we reported a novel crosstalk of ARF/β-catenin dysregulated YAP in Hippo pathway and a new approach to stimulate ARF-mediated signaling to inhibit nuclear YAP using nanomaterials implicating an innovative avenue for treatment of cancer.
- Subjects :
- 0301 basic medicine
Male
Epithelial-Mesenchymal Transition
lcsh:Medicine
Cell Cycle Proteins
Protein Serine-Threonine Kinases
Article
03 medical and health sciences
Mice
PTEN
Animals
Nanotechnology
Hippo Signaling Pathway
Cyclin-Dependent Kinase Inhibitor p19
lcsh:Science
Protein kinase B
Transcription factor
Wnt Signaling Pathway
PI3K/AKT/mTOR pathway
Adaptor Proteins, Signal Transducing
Cell Nucleus
Gene knockdown
Hippo signaling pathway
Multidisciplinary
Microscopy, Confocal
biology
Tea
Chemistry
lcsh:R
Wnt signaling pathway
Prostatic Neoplasms
YAP-Signaling Proteins
Phosphoproteins
Carbon
Cell biology
030104 developmental biology
Cancer cell
biology.protein
lcsh:Q
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....46290b7c319f0917c776801cb37cbd55