DIO2 induces epithelial-mesenchymal transition to enhance gastric cancer metastasis through the VEGF signaling pathway

This study aims to investigate the clinical significance of Deiodinase 2 (DIO2) in gastric cancer (GC) and elucidate the molecular mechanisms by which it modulates the VEGF-driven epithelial-mesenchymal transition (EMT) axis. This investigation seeks to uncover the molecular mechanisms driving GC metastasis, establishing DIO2 as a viable theoretical foundation for the development of targeted therapies. Integrated bioinformatics analysis involving GEO and TCGA datasets was initially performed to assess DIO2 expression levels and their correlation with patient prognosis. Subsequently, the impact of DIO2 overexpression on the malignant phenotypes of GC cells (AGS and HGC-27) was examined in vitro, with Bevacizumab (Bev) utilized to intercept the VEGF pathway. Finally, xenograft mouse models were established to validate the oncogenic role of DIO2 in vivo. Bioinformatic analysis identified DIO2 as a key regulator in angiogenic pathways, pointing toward a VEGF-mediated mechanism. We demonstrated that DIO2 overexpression promotes aggressive GC phenotypes, including increased proliferation and motility, while its inhibition effectively abrogates these pro-tumorigenic traits. Further investigation revealed that DIO2 exerts its functions by triggering the synergistic activation of VEGF signaling and the EMT process. Our evidence indicates that DIO2 serves as a reliable prognostic biomarker for GC. Mechanistically, it exerts a crucial role in augmenting the proliferative and metastatic potential of GC cells via the stimulation of VEGF signaling and the subsequent EMT process.