Fig. 1.

Schematic representation of EpCAM expression throughout tumor progression. a EpCAM is strongly expressed in most carcinomas, associates with an epithelial phenotype, and regulates proliferation. b Initial phases of local invasion are characterized by epithelial-to-mesenchymal transition with a loss of EpCAM expression at the plasma membrane (EpCAM^high to EpCAM^low), a gain of migratory and invasive capacity, and a mesenchymal phenotype. c, d Invasive tumor cells gain access to the blood or lymph stream upon intravasation and begin to circulate in the body. These circulating tumor cells have a mesenchymal, rather quiescent phenotype. Circulating tumor cells leave the blood or lymph stream (extravasation) and invade secondary organs at locoregional or distant sites. e Disseminated tumor cells generate novel malignant seeds and develop into micrometastases. f Micrometastases perform a mesenchymal-to-epithelial transition, re-express EpCAM, regain proliferative capacity, and grow to form macro-metastases