USP47 enhances NRP1-mediated angiogenesis to promote gastric cancer progression

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-06-09 DOI:10.1016/j.bbamcr.2025.120004

Wei Chen , Huizhi Wang , Haitao Sun , Junbo Zuo , Pengcheng Jiang , Wen Feng , Zhenhua Huang

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Abstract

Gastric cancer (GC) is a leading cause of cancer-related mortality, particularly in East Asia, where its incidence remains high. The limited prognosis for advanced GC patients underscores the need for new therapeutic strategies targeting key molecules involved in tumor progression. In this study, we investigated the role of the deubiquitinating enzyme USP47 in GC progression, focusing on its interaction with Neuropilin-1 (NRP1), a co-receptor known to enhance angiogenesis. Our findings reveal that USP47 is significantly overexpressed in GC tissues and correlates with poor patient survival. Through in vitro experiments, we demonstrate that USP47 promotes GC cell proliferation, migration, and invasion. Additionally, USP47 enhances angiogenesis by stabilizing NRP1, preventing its ubiquitination and degradation, and activating the PI3K/Akt signaling pathway. These results suggest that USP47 contributes to GC progression through the regulation of NRP1-mediated angiogenesis, highlighting its potential as a therapeutic target for GC treatment.

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USP47增强nrp1介导的血管生成促进胃癌进展

胃癌（GC）是癌症相关死亡的主要原因，特别是在东亚，其发病率仍然很高。晚期胃癌患者的预后有限，因此需要针对参与肿瘤进展的关键分子开发新的治疗策略。在这项研究中，我们研究了去泛素化酶USP47在GC进展中的作用，重点研究了它与Neuropilin-1 （NRP1）的相互作用，NRP1是一种已知的促进血管生成的共受体。我们的研究结果显示，USP47在胃癌组织中显著过表达，并与患者生存不良相关。通过体外实验，我们证明USP47促进GC细胞的增殖、迁移和侵袭。此外，USP47通过稳定NRP1、阻止其泛素化和降解、激活PI3K/Akt信号通路来促进血管生成。这些结果表明，USP47通过调控nrp1介导的血管生成来促进GC的进展，突出了其作为GC治疗靶点的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et biophysica acta. Molecular cell research 生物-生化与分子生物学

CiteScore

10.00

自引率

2.00%

发文量

151

审稿时长

44 days

期刊介绍： BBA Molecular Cell Research focuses on understanding the mechanisms of cellular processes at the molecular level. These include aspects of cellular signaling, signal transduction, cell cycle, apoptosis, intracellular trafficking, secretory and endocytic pathways, biogenesis of cell organelles, cytoskeletal structures, cellular interactions, cell/tissue differentiation and cellular enzymology. Also included are studies at the interface between Cell Biology and Biophysics which apply for example novel imaging methods for characterizing cellular processes.