TY - JOUR
T1 - Dysregulation of YAP by ARF Stimulated with Tea-derived Carbon Nanodots
AU - Xie, Yingqiu
AU - Sun, Qinglei
AU - Nurkesh, Ayan A.
AU - Lu, Jiang
AU - Kauanova, Sholpan
AU - Feng, Jinhong
AU - Tursynkhan, Darkhan
AU - Yang, Qing
AU - Kassymbek, Aishabibi
AU - Karibayev, Mirat
AU - Duisenova, Korlan
AU - Fan, Haiyan
AU - Wang, Xiao
AU - Manarbek, Limara
AU - Maipas, Aisulu
AU - Chen, Zhenbang
AU - Balanay, Mannix P.
N1 - Funding Information:
This work is supported in part by China-Kazakhstan collaboration grant (No. CK-07-09) to Dr. Yingqiu Xie and the Nazarbayev University Social Policy grant of Dr. Fan (HFan-01-10-2016). We would like to thank Nazarbayev University undergraduate students Aidarkhan Izimov, Aiya Yesbolatova and Teaching Assistant Nurlan Mansurov for kind assistance on the experiment. As one of the experiments is designed for graduate course teaching of BIOL 501-Fundamentals of Biological Sciences, we also would like to thank graduate students of Akerke Abdirakhman, Anton Borissenko, Aidana Sheryazdanova, Aliya Stanova, Tleubek Yeleussizov, Gaukhar Zhurgenbayeva for the participation of the course learning.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-017-16441-y
DO - 10.1038/s41598-017-16441-y
M3 - Article
AN - SCOPUS:85036516487
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 16441
ER -
