Identification of Novel Small Molecule Inhibitors (SMI) of YAP/TAZ Oncoproteins in Breast Cancer Using HiBiT Bioluminescent Biosensors
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Authors
Wu, Liqing
Date
Type
thesis
Language
eng
Keyword
YAP , TAZ , Breast Cancer , Biosensor , Bioluminescence
Alternative Title
Abstract
Breast cancer (BC) is the most frequently diagnosed cancer among females, accounting for 25% of all cancer cases worldwide. Among all the subtypes of BC, triple negative breast cancer (TNBC) is considered one of the most-deadly killers in the world, characterized by its increasing incidence and poor prognosis, which demands improved targeted therapy urgently. Recently the Hippo signaling pathway has emerged as an important cellular network mediating tumorigenesis, drug resistance and cancer metastasis. Current evidence indicates that the core Hippo components YAP and its paralog TAZ are involved in the tumorigenesis and metastasis of TNBC. Therefore, targeting YAP/TAZ may be a promising strategy for TNBC therapy. However, few YAP/TAZ-targeted drugs have been identified and no YAP/TAZ-targeted drug has been used for clinical cancer treatment.
In my thesis project, I hypothesize that the Hippo pathway, especially the Hippo output mediators YAP/TAZ can play a central role in the development, metastasis, drug resistance of TNBC; and are therefore potential “druggable” targets for TNBC therapy. To test this hypothesis, the following specific objectives will be carried out:
1. Establishment of HiBiT-tagged YAP/TAZ bioluminescent biosensors in monitoring YAP/TAZ levels in cells
2. Screen for small molecules regulating the stability of YAP/TAZ in TNBC cells
3. Characterization of small molecules targeting YAP/TAZ in TNBC cells
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ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.