Han, Jisoo Shin, Yoon-Hee Kim, Eunjung Park, Hyun-Mee Kim, Jae-Young 2025-03-22T12:00:16Z 2025-03-22T12:00:16Z 2025-03-19 2025-02 1535-3893 https://pubs.kist.re.kr/handle/201004/151979 The E3 ubiquitin ligase neural precursor cell-expressed developmentally down-regulated 4 (NEDD4) is involved in various cancer signaling pathways, including PTEN/AKT. However, its role in promoting gastric cancer (GC) progression is unclear. This study was conducted to elucidate the role of NEDD4 in GC progression. We found that the inhibition of NEDD4 expression significantly reduced the migratory and proliferative abilities of GC cells, with minimal impact on the PTEN expression or p-AKT activation, suggesting that NEDD4 may exert its GC-promoting effects through alternative pathways. To gain novel insights into the role of NEDD4 in GC, we performed a comprehensive proteomic analysis to search for proteins with altered expression levels following NEDD4 gene knockdown, identifying a total of 3916 proteins. Pathway analysis of differentially expressed proteins (DEPs) indicated the potential involvement of NEDD4 in cancer-related metabolic pathways. Furthermore, the protein-protein interaction network of the DEPs revealed enriched core modules, highlighting key cellular processes and signaling pathways regulated by NEDD4 in GC. Additionally, we identified proteins whose expression was altered by NEDD4 inhibition, some of which were associated with poor prognosis in GC. These findings suggest that these proteins may act as downstream effectors that contribute to NEDD4-mediated GC progression. English American Chemical Society Proteomic Characterization of NEDD4 Unveils Its Potential Novel Downstream Effectors in Gastric Cancer Article 10.1021/acs.jproteome.4c01109 1 Journal of Proteome Research, v.24, no.2, pp.891 - 902 Journal of Proteome Research 24 2 891 902 N scie scopus 001408099000001 2-s2.0-85216680288 Biochemical Research Methods Biochemistry & Molecular Biology Article E3 UBIQUITIN LIGASES C-KINASE SUBSTRATE COLORECTAL-CANCER CELL-MIGRATION UP-REGULATION EXPRESSION MARCKS GROWTH REGULATOR PROGNOSIS NEDD4 proteomics gastric cancer