Although it has been reported that REG4 induces a series of anti-apoptosis gene expression through activating epidermal growth factor receptor (EGFR)/ protein kinase B (AKT)/ activator protein 1 (AP-1) signaling pathway [10], and that REG4 also increases mitogenesis involving AKT/ glycogen synthase kinase 3 beta (GSK3beta)/beta-Catenin/ transcription factor 4 (TCF-4) signaling in human colorectal cancer [11], no thorough investigation about the mechanism of peritoneal metastasis has been conducted, neither its receptor, nor its interactive partner has been identified for more than a decade. The gene discussed is EGFR; the disease is colorectal cancer.