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Updated: Dec 28, 2025
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Published on: July 20, 2014
EPS8L3 promotes hepatocellular carcinoma proliferation and metastasis by modulating EGFR dimerization and
Zefeng Xuan1,2,3,4,5, Long Zhao1,2,3,4,5, Zequn Li1,2,3,4,5
1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou 310003, China.
Abstract:
As a member of epidermal growth factor receptor (EGFR) kinase substrate 8 (EPS8) family, the role of EPS8 like 3 protein (EPS8L3) has not been well studied in malignancies. However, EPS8 has been reported to be associated with prognosis and functions in several kinds of cancers. Hence, whether EPS8L3 plays similar roles in the tumorigenesis of human cancers, especially in hepatocellular carcinoma (HCC), is still needed to be further explored. In this study, we revealed that EPS8L3 was overexpressed in HCC tissues compared with adjacent non-tumor tissues, and was associated with a poor clinical prognosis. Both in vitro and in vivo experiments showed that EPS8L3 could promote the proliferative ability by downregulating p21/p27 expression, and promote the migratory and invasive abilities by upregulating matrix metalloproteinase-2 expression. Furthermore, we demonstrated that EPS8L3 could affect the activation of the EGFR-ERK pathway by modulating EGFR dimerization and internalization, which may not depend on the formation of EPS8L3-SOS1-ABI1 complex. Taken together, our study showed that EPS8L3 plays a pivotal role in the tumorigenesis and progression of HCC, and it might be a potential therapeutic target for HCC.
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