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EMP2 promotes hepatocellular carcinoma proliferation and invasion by activating cellular autophagy

HAIYING PANG1,#, FENGBO WU1,#, YU ZHANG1, NAN ZHANG2, CHUNTING WANG1, QIU LI1, GU HE1,*, PENG ZHANG3,*
1 Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
2 State Key Laboratory of Southwestern Chinese Medicine Resources, College of Medical Technology and School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
3 Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
* Corresponding Author: GU HE. Email: email; PENG ZHANG. Email: email
(This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)

Oncology Research https://doi.org/10.32604/or.2024.043948

Received 17 July 2023; Accepted 13 May 2024; Published online 11 June 2024

Abstract

Background: EMP2 is a tumor-associated membrane protein belonging to the GAS-3/PMP22 gene family. EMP2 expression demonstrates significant tissue specificity and heterogeneity in various human tissues and tumor tissues, where it may play a role in either promoting or inhibiting tumor growth. This study aimed to investigate the expression level, biological functions, and molecular mechanisms of EMP2 in liver cancer. Methods: we analyzed the mRNA expression levels of EMPs family genes in hepatocellular carcinoma (HCC) tissues and normal liver tissues based on the TCGA database and immunohistochemical analysis of tissue microarrays. Subsequently, we constructed HCC cell lines with either knockdown or overexpression of EMP2 to examine the biological functions and molecular mechanisms of EMP2 in tumorigenesis in vivo and in vitro. Results: Bioinformatic and immunohistochemical analysis of tissue microarrays have confirmed the significant upregulation of EMP2 in HCC tissues. In vitro and in vivo studies have shown that downregulation of EMP2 results in a moderate reduction in the proliferation and invasive capacity of HCC cells. Conversely, overexpression of EMP2 enhances the invasive capacity of HCC cells and induces autophagy. Initial investigations into the molecular mechanisms underlying EMP2-mediated enhancement of HCC cell invasion have revealed the dual regulation of EMP2-induced autophagy and the integrin pathway, which synergistically influence the invasive and metastatic potential of HCC cells. Conclusion: EMP2 holds promise as a diagnostic marker for HCC metastasis and a potential target for targeted therapy.

Graphical Abstract

EMP2 promotes hepatocellular carcinoma proliferation and invasion by activating cellular autophagy

Keywords

Epithelial membrane protein 2; Hepatocellular carcinoma; Autophagy; Integrin pathway
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