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Updated: May 30, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Proteomic Characterization of NEDD4 Unveils Its Potential Novel Downstream Effectors in Gastric Cancer
Jisoo Han1, Yoon-Hee Shin2, Eunjung Kim3
1Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon 34134, Republic of Korea.
Abstract:
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.
Insights
Neural precursor cell-expressed developmentally down-regulated 4 (NEDD4) inhibition reduced gastric cancer cell migration and proliferation. Proteomic analysis revealed NEDD4 regulates cancer-related metabolic pathways and identifies potential downstream effectors in GC progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The E3 ubiquitin ligase NEDD4 (neural precursor cell-expressed developmentally down-regulated 4) is implicated in cancer signaling pathways like PTEN/AKT.
- Its specific role in promoting gastric cancer (GC) progression remains largely undefined.
Purpose of the Study:
- To investigate the function of NEDD4 in the progression of gastric cancer.
- To identify novel molecular mechanisms and downstream targets of NEDD4 in GC.
Main Methods:
- NEDD4 expression was inhibited in GC cells to assess effects on migratory and proliferative abilities.
- Comprehensive proteomic analysis was performed on NEDD4-knockdown GC cells to identify differentially expressed proteins (DEPs).
- Pathway and protein-protein interaction network analyses were conducted on DEPs.
Main Results:
- NEDD4 inhibition significantly decreased GC cell migration and proliferation, independent of PTEN expression or p-AKT activation.
- Proteomic analysis identified 3916 proteins with altered expression upon NEDD4 knockdown.
- Pathway analysis linked NEDD4 to cancer-related metabolic pathways, and network analysis highlighted key regulated processes. Several identified proteins correlated with poor GC prognosis.
Conclusions:
- NEDD4 promotes gastric cancer progression through pathways distinct from PTEN/AKT.
- NEDD4 regulates cancer-associated metabolic pathways and cellular processes in GC.
- Proteins identified by proteomic analysis represent potential downstream effectors mediating NEDD4's role in GC progression and may serve as prognostic biomarkers.
