EMP2 promotes hepatocellular carcinoma proliferation and invasion by activating cellular autophagy

Sep 23, 2026

Uploaded by Finn

EMP2 is a tumor-associated membrane protein in the GAS-3/PMP22 family with tissue-specific heterogeneity that may influence tumor growth. The study examined EMP2 expression and its molecular functions in hepatocellular carcinoma using TCGA-based analyses, immunohistochemical tissue microarrays, and HCC cell models with EMP2 knockdown or overexpression. Results showed EMP2 upregulation in HCC, where reduction modestly decreased proliferation and invasion, while overexpression promoted invasion and induced autophagy via regulation of the integrin pathway.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Introduction

Integrin signaling and EMP2

Methods

Results

Conclusion

ONCOLOGY RESEARCH 2025 33(2): 443-464 ARTICLE EMP2 promotes hepatocellular carcinoma proliferation and invasion by activating cellular autophagy HAIYING PANG 1,\#; FENGBO WU 1,\#; YU ZHANG 1; NAN ZHANG2; CHUNTING WANG 1; QIU LI 1; GU HE 1,*; 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 Key words: Epithelial membrane protein 2, Hepatocellular carcinoma, Autophagy, Integrin pathway 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 themRNA 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. Introduction Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, with particularly high incidence rates in Eastern Asia and Sub-Saharan Africa [1,2] . For early-stage HCC, Surgical resection, local ablation, or liver transplantation are the standard treatment options, resulting in a ﬁve-year survival rate of over 70% [2,3] . However, due to the absence of signs and symptoms in early-stage HCC, the disease is frequently diagnosed at an advanced stage [4] . Although tyrosine kinase inhibitors *Address correspondence to: Gu He, [heguscu@163.com](heguscu@163.com); Peng Zhang, [izhangpeng@163.com](izhangpeng@163.com) \#These authors contributed equally Received: 17 July 2023; Accepted: 13 May 2024; Published: 16 January 2025 (TKIs), such as sorafenib and lenvatinib, and immune checkpoint inhibitors (ICIs), like atezolizumab and Ipilimumab, have demonstrated efﬁcacy as treatment options for unresectable HCC, the development of resistance to conventional chemotherapy ultimately results in a poor prognosis [4,5] . Thus, elucidating the molecular mechanisms involved in HCC tumorigenesis and development, as well as identifying novel molecular targets for HCC treatment and prognosis, is of paramount importance. Integrins, a diverse family of cell membrane adhesion receptors, modulate the invas

FAQs

What relationship does EMP2 have with hepatocellular carcinoma in this study?

EMP2 is significantly upregulated in hepatocellular carcinoma tissues. Functional experiments indicate that altering EMP2 levels changes tumor cell proliferation and invasive behavior.

How did the researchers test EMP2’s role experimentally?

They used TCGA analyses and immunohistochemical examination of tissue microarrays, then constructed HCC cell lines with EMP2 knockdown or overexpression to study effects in vitro and in vivo.

What mechanism connects EMP2 to increased invasion?

The study reports that EMP2 enhances HCC cell invasion through dual regulation of autophagy and the integrin pathway, which jointly affect invasive and metastatic potential.

Sep 23, 2026

Uploaded by Finn