EpCAM duality becomes this molecule in a new Dr. Jekyll and Mr. Hyde tale.

EpCAM, known as an epithelial cell adhesion molecule, plays an essential role in cell adhesion, migration, metastasis and cell signalling. Rather than acting as an apoptosis antagonist, it induces cellular proliferation that impacts the cell cycle, and as a signalling transducer it uses and enhances the Wnt pathway, which is significantly relevant in cell renewal and cancer. EpCAM has become a marker of circulating tumour cells (CTCs) in lung cancer due to its specificity, and its high and stable expression level. Recent findings have allowed us to relearn and discover EpCAM again as a CSCs marker by demonstrating its role in human epithelial cancer progression. In line with this, the focus of attention on EpCAM has become an appealing therapeutic target, although the literature shows a clear controversy in information about its clinical significance. Despite this contradictory fact, solid evidence has demonstrated its dual role as a molecule with oncogenic and tumour suppressor properties, in which the microenvironment is influential. Therefore, its dual role appears to be both tissue- and tumour- dependent. In this review, we summarised the novel and updated insights in the EpCAM field by simplifying the understanding of the biological role of this fascinating molecule, and by showing the promising therapeutic tools that have been developed by various approaches which use antibodies and vaccines for different cancer types for the clear purpose of improving patient outcome.