Our previous study observed that the HECT E3 ubiquitin ligase NEDD4 is significantly correlated with tumor metastasis and required for migration and invasion signaling of EGFR in gastric cancer cells.
The Nedd4 family E3 ligases Itch and WWP1/2 play crucial roles in the regulation of cell cycle progression and apoptosis and are closely correlated with cancer development and metastasis.
Stability of NEDD4-1, in turn, is tightly controlled by a 34 kDa oncoprotein, p34<sup>SEI-1</sup> and it regulates PTEN degradation and activates PI3K/AKT pathway, resulting in cancer metastasis. p34<sup>SEI-1</sup> affects not only the expression of NEDD4-1 during transcription and translation but also the subcellular localization of PTEN.
Our findings indicate that NEDD4 potentially plays a critical role in activating the PI3K/AKT signaling pathway by negatively regulating PTEN levels in PDAC cells, which promotes pancreatic cancer cell proliferation and metastasis.
Our results indicate that Nedd4-1 is an exceptional prognostic biomarker for GCA and suggest that Nedd4-1 may play an essential role in GCA metastasis.