The tumor-associated EpCAM regulates morphogenetic movements through intracellular signaling

Epithelial cell adhesion molecule (EpCAM) is best known as a tumor associated protein highly ex pressed in carcinomas The function of this cell surface protein during embryonic development and its potential role in cancer are still poorly understood We identified EpCAM in a gain-of-function screen for inducers of abnormal tissue mixing during gastrulation Elevated EpCAM levels in either the ectoderm or the mesoderm con fer "invasive" properties to cells in both populations We found that this phenotype represents an "overstimulation" of an essential activity of EpCAM in controlling cell movements during embryonic development Surprisingly, this property is independent of the putative adhesive function of EpCAM, and rather relies on a novel signaling function that operates through down regulation of PKC activity We show that inhibition of novel PKCs accounts entirely for the invasive phenotype induced by abnormally high levels of EpCAM as well as for its nor mal function in regulating cell rearrangement during early development