Figure 1: SPINK1 promotes epithelial-mesenchymal transition (EMT) through EGFR signaling pathway in PCa as a growth factor. SPINK1 binds to EGFR as a autocrine growth factor. There are at least three signaling pathways downstream of EGFR, including the PI3K/AKT, JAK/STAT, and MAPK/MEK/ERK signaling pathway. All three downstream targets are phosphorylated by SPINK1 and EGF. However, the MAPK/MEK/ ERK pathway is actually mainly involved in SPINK1-induced epithelialmesenchymal transition (EMT).