Role of Ca ²⁺ ‐Dependent Epithelial‐Mesenchymal Transition in Malignant Progression of Colorectal Cancer: Special Focus on <scp>REG</scp> Iα/ <scp>EDNRB</scp>

BACKGROUND: Colorectal cancer (CRC) is a major global health problem, ranking as the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths. This study aimed to elucidate the role and underlying molecular mechanism of the Regenerating Islet-Derived Protein 1 Alpha (REG Iα)/Endothelin Receptor B (EDNRB) axis in CRC malignant progression. METHODS: chelator BAPTA-AM. Cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) were assessed using Western blotting, RT-qPCR, and Transwell assays. RESULTS: /CaMKII signaling pathway, triggering endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) accumulation to induce apoptosis. Importantly, overexpression of EDNRB rescued the malignant phenotypes suppressed by REG Iα knockdown, whereas BAPTA-AM treatment abolished this rescue effect. The REG Iα/EDNRB axis was further demonstrated to drive the EMT process, and these findings were validated in vivo. CONCLUSIONS: -dependent epithelial-mesenchymal transition, suggesting that targeting this axis is a promising therapeutic strategy to inhibit CRC metastasis.