biostudies-literatureYan LNational Natural Science Foundation of China (National Science Foundation of China)889https://www.ebi.ac.uk/biostudies/studies/S-EPMC12706015biostudies-literatureUnknown16(1)The enhanced adhesion between gastric cancer (GC) cells and peritoneal mesothelial cells (PMCs) is one of the key factors in the formation of the pre-peritoneal-metastasis adaptive microenvironment. USP35 belongs to the ubiquitin-specific protease family and is involved in regulating the occurrence and progression of various diseases. However, whether this gene can regulate the adhesion of GC cells to PMCs has not been clarified. The aim of this study was to identify the mechanism by which USP35 promotes the formation of the pre-peritoneal-metastasis adaptive microenvironment of GC and to find potential therapeutic targets. For the first time, we found that USP35 expression is upregulated in GC tissues, especially in peritoneal metastatic nodules, and is associated with poor prognosis. USPCell death & diseaseDe-ubiquitinase USP35 promotes peritoneal dissemination of gastric cancer by regulating metabolic reprogramming.PMC12706015No.82573305No.82203818Peng XYan LWu LChen MLi FCai LLi RZou DZhang YMei JLiu AGao XWang YfalseDe-ubiquitinase USP35 promotes peritoneal dissemination of gastric cancer by regulating metabolic reprogramming.The enhanced adhesion between gastric cancer (GC) cells and peritoneal mesothelial cells (PMCs) is one of the key factors in the formation of the pre-peritoneal-metastasis adaptive microenvironment. USP35 belongs to the ubiquitin-specific protease family and is involved in regulating the occurrence and progression of various diseases. However, whether this gene can regulate the adhesion of GC cells to PMCs has not been clarified. The aim of this study was to identify the mechanism by which USP35 promotes the formation of the pre-peritoneal-metastasis adaptive microenvironment of GC and to find potential therapeutic targets. For the first time, we found that USP35 expression is upregulated in GC tissues, especially in peritoneal metastatic nodules, and is associated with poor prognosis. USP2025-01-01T00:00:00Z2025 Dec2026-06-06T03:49:37.506Z2026-05-25T03:12:01.096ZS-EPMC127060154137213410.1038/s41419-025-08322-4