Biochimica et biophysica acta. Molecular cell research · 2025
USP47 enhances NRP1-mediated angiogenesis to promote gastric cancer progression.
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Chen Wei, Wang Huizhi, Sun Haitao, Zuo Junbo, Jiang Pengcheng, Feng Wen, Huang Zhenhua
Аннотация
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.
Предметные рубрики MeSH
HumansStomach NeoplasmsNeovascularization, PathologicNeuropilin-1Ubiquitin ThiolesteraseCell ProliferationDisease ProgressionCell Line, TumorCell MovementSignal TransductionUbiquitinationAnimalsMaleMiceFemaleGene Expression Regulation, NeoplasticProto-Oncogene Proteins c-aktPhosphatidylinositol 3-KinasesAngiogenesis