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Dysregulation of YAP by ARF Stimulated with Tea-derived Carbon Nanodots
Yingqiu Xie1, Qinglei Sun2, Ayan A Nurkesh3
1Department of Biology, School of Science and Technology, Nazarbayev University, Astana, 010000, Kazakhstan. yingqiu.xie@nu.edu.kz.
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.
Insights
This study reveals how ARF protein influences YAP
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The Hippo pathway's downstream transcription factor, YAP, is crucial for development and homeostasis.
- YAP's role in prostate cancer is linked to Pten/Trp53 inactivation and ARF elevation, suggesting crosstalk with AKT/mTOR/YAP and ARF.
- The precise function and cellular trafficking of YAP in cancer remain incompletely understood.
Purpose of the Study:
- To elucidate the detailed function and trafficking of YAP in cancer cells.
- To investigate the regulatory mechanisms of YAP by ARF within the Hippo and Wnt pathways.
- To explore the potential of nanomaterials in modulating ARF-mediated signaling for cancer treatment.
Main Methods:
- Utilized a genetic engineered mouse (GEM) microarray model.
- Performed ARF knockdown experiments to assess YAP localization and F-actin.
- Investigated protein turnover of β-catenin/YAP and AKT activity.
- Examined the interaction of tea-derived carbon dots with ARF.
Main Results:
- ARF was found to dysregulate the Hippo and Wnt pathways.
- ARF knockdown led to reduced non-nuclear YAP localization and increased F-actin.
- ARF knockdown suppressed β-catenin/YAP protein turnover, enhancing AKT activity and YAP phosphorylation.
- Tea-derived carbon dots interacted with nuclear ARF, potentially promoting YAP non-nuclear localization.
Conclusions:
- A novel crosstalk between ARF, β-catenin, and YAP in the Hippo pathway was identified.
- ARF dysregulation impacts YAP's cellular localization and activity.
- Nanomaterials offer a new strategy to target ARF-mediated signaling, inhibiting nuclear YAP for cancer therapy.
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