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上皮膜蛋白2通过激活细胞自噬促进肝细胞癌的增殖和侵袭。

EMP2 promotes hepatocellular carcinoma proliferation and invasion by activating cellular autophagy.

作者信息

Pang Haiying, Wu Fengbo, Zhang Y U, Zhang Nan, Wang Chunting, Li Qiu, He G U, Zhang Peng

机构信息

Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.

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.

出版信息

Oncol Res. 2025 Jan 16;33(2):443-464. doi: 10.32604/or.2024.043948. eCollection 2025.

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 and .

RESULTS

Bioinformatic and immunohistochemical analysis of tissue microarrays have confirmed the significant upregulation of EMP2 in HCC tissues. and 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.

摘要

背景

EMP2是一种肿瘤相关膜蛋白,属于GAS-3/PMP22基因家族。EMP2的表达在各种人体组织和肿瘤组织中表现出显著的组织特异性和异质性,在其中它可能在促进或抑制肿瘤生长中发挥作用。本研究旨在探究EMP2在肝癌中的表达水平、生物学功能及分子机制。

方法

我们基于TCGA数据库以及组织芯片的免疫组化分析,分析了肝细胞癌(HCC)组织和正常肝组织中EMPs家族基因的mRNA表达水平。随后,我们构建了EMP2敲低或过表达的HCC细胞系,以研究EMP2在肿瘤发生中的生物学功能和分子机制。

结果

组织芯片的生物信息学和免疫组化分析证实了EMP2在HCC组织中显著上调。 以及 研究表明,EMP2的下调导致HCC细胞的增殖和侵袭能力适度降低。相反,EMP2的过表达增强了HCC细胞的侵袭能力并诱导自噬。对EMP2介导的HCC细胞侵袭增强的分子机制的初步研究揭示了EMP2诱导的自噬和整合素途径的双重调节,它们协同影响HCC细胞的侵袭和转移潜能。

结论

EMP2有望成为HCC转移的诊断标志物和靶向治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed11/11754002/22bd3ce4085c/OncolRes-33-43948-f001.jpg

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