Zhang, Ziqian
(2020)
YAP/TAZ-Inhibitor-Based Drug Delivery System for Cancer Therapy.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
The YES-associated protein (YAP) and the transcriptional co-activator with PDZ-binding motif (TAZ) are two important transcriptional co-activators in the Hippo signaling pathway, which play an essential role in organ size control, tumor suppression, tissue regeneration and stem cell self-renewal. However, aberrant activation of YAP and TAZ due to deregulation of the Hippo pathway or overexpression of YAP/TAZ and TEADs can promote cancer development. Hence, pharmacological inhibition of YAP and TAZ may be a useful approach to treat tumors with high YAP/TAZ activity. Here, we developed a YAP/TAZ-inhibitor (niflumic acid (NA))-based drug delivery system for enhanced cancer therapy. Through disrupting the interaction between the TEA domain transcription factors (TEADs) and YAP/TAZ, NA reduces the expression of downstream genes that promote tumor proliferation and migration. At the same time, other hydrophobic anti-cancer drug can be co-delivered to tumor site to improve the overall antitumor activity and decrease side effect. Our strategy may not only improve delivery of well-established anti-cancer drugs, but also further improve their efficacy through inhibiting YAP/TAZ activity.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
9 April 2020 |
| Date Type: |
Publication |
| Defense Date: |
3 April 2020 |
| Approval Date: |
9 April 2020 |
| Submission Date: |
7 April 2020 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
41 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
YAP ;TAZ; TEAD; Niflumic Acid; Dasatinib |
| Date Deposited: |
09 Apr 2020 11:30 |
| Last Modified: |
09 Apr 2020 11:30 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/38605 |
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