Targeting EphA2 Suppresses Hepatocellular Carcinoma Initiation and Progression by Dual Inhibition of JAK1/STAT3 and AKT Signaling

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2021 Feb 24

PMID 33626345

Citations 20

Authors

Hao Wang

Wei Hou

Aldeb Perera

Carlee Bettler

Jordan R Beach

Xianzhong Ding

Jun Li

Mitchell F Denning

Asha Dhanarajan

Scott J Cotler

Cara Joyce

Jun Yin

Fowsiyo Ahmed

Lewis R Roberts

Wei Qiu

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) remains one of the deadliest malignancies worldwide. One major obstacle to treatment is a lack of effective molecular-targeted therapies. In this study, we find that EphA2 expression and signaling are enriched in human HCC and associated with poor prognosis. Loss of EphA2 suppresses the initiation and growth of HCC both in vitro and in vivo. Furthermore, CRISPR/CAS9-mediated EphA2 inhibition significantly delays tumor development in a genetically engineered murine model of HCC. Mechanistically, we discover that targeting EphA2 suppresses both AKT and JAK1/STAT3 signaling, two separate oncogenic pathways in HCC. We also identify 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.

Citing Articles

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