Date of Award
2020
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biological Science
Abstract
Hepatocellular Carcinoma (HCC) remains one of the deadliest malignancies worldwide. One major obstacle to treatment is a lack of effective molecular-targeted therapies. Here, we identify EphA2 receptor tyrosine kinase as a clinically relevant target for HCC. EphA2 expression and signaling is enriched in human HCC and associates with poor prognosis. Loss of EphA2 suppressed the initiation and growth of HCC in vitro and in vivo. Furthermore, CRISPR/CAS9 mediated EphA2 inhibition significantly delayed tumor development in a genetically-engineered murine model of HCC. Mechanistically, we discovered that targeting EphA2 simultaneously suppresses both JAK1/STAT3 and AKT signaling, two separate oncogenic pathways in HCC. We also identified a small molecule kinase inhibitor of EphA2 that suppresses tumor progression in a murine HCC model. Together, our results suggest EphA2 as a promising therapeutic target for HCC.
Recommended Citation
Wang, Hao, "Targeting EPHA2 in Hepatocellular Carcinoma: Uncovering Its Therapeutic Potential and Beyond" (2020). Dissertations. 3831.
https://ecommons.luc.edu/luc_diss/3831
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Copyright Statement
Copyright © 2020 Hao Wang
