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USP47 enhances NRP1-mediated angiogenesis to promote gastric cancer progression
Wei Chen1, Huizhi Wang2, Haitao Sun3
1Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201600, China.
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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