Roles of Na+/Ca2+ exchanger 1 in digestive system physiology and pathophysiology

Figure 2 The regulated signal pathways and transcription factors of NCX1 in digestive diseases. Transforming growth factor-β (TGF-β) stimulates the activation of PLC-IP3 and Ca²⁺ release from the endoplasmic reticulum, which activates TRPC1 and the reverse mode of NCX1 resulting in Ca²⁺ influx, and the increase of Ca²⁺ mediates cell motility directly or indirectly via activation of Ca²⁺-dependent PKC in pancreatic cancer. Cerulein activates NCX1 and induces activation of inflammatory factors TNF-α and IL-6 and the downstream NK-κB pathway in pancreatic cells. TGF-β can upregulate the expression of NCX1 and TRPC6 and activate the downstream SMAD pathway to regulate the migration and invasion of hepatocellular carcinoma cells.