Date of Graduation
5-2016
Document Type
Dissertation (PhD)
Program Affiliation
Cancer Biology
Degree Name
Doctor of Philosophy (PhD)
Advisor/Committee Chair
Mien-Chie Hung
Committee Member
Dihua Yu
Committee Member
Ann-Bin Shyu
Committee Member
Dos D. Sarbassov
Committee Member
Li Ma
Abstract
The Yes-associated protein (YAP) is an effector that transduces the output of the Hippo pathway to transcriptional modulation. Considering the role of YAP in cancers, this protein has emerged as a key node in malignancy development. In this study, we determined that Aurora A kinase acts as a positive regulator for YAP-mediated transcriptional machinery. Specifically, YAP associates with Aurora A predominantly in the nucleus. Activation of Aurora A can impinge on YAP activity through direct phosphorylation. Moreover, aberrant expression of YAP and Aurora A signaling is highly correlated with triple-negative breast cancer (TNBC). We herein provide evidence to establish the functional relevance of this newly discovered regulatory axis in TNBC. This study not only has advanced the understanding of the intricate network of YAP in cancers but also has revealed a potential route to intervene oncogenic YAP function.
Keywords
YAP, Aurora, Phosphorylation, Transcription, Breast Cancer