EPCAM and neoplasm: Previous studies showed that EpCAM intracellular domain could promote tumorigenesis in tumor initiation cells (TICs) through the up-regulation of reprogramming genes and the epithelial-mesenchymal transition (EMT), and release of its extracellular domain could further enhance EpCAM cleavage and trigger its intracellular domain-mediated signaling in an autocrine or paracrine manner, consequently leading to tumor initiation and progression (Brown et al., 2021; Endaya et al., 2017).