Regulatory roles of grass carp EpCAM in cell morphology, proliferation and migration

Epithelial cell adhesion molecule (EpCAM) is a Ca(2+)-independent and relatively weak adhesion molecule, which has been extensively investigated in mammalian models. However, the functional roles of its fish homolog are largely unknown. In the present study, we explored the biological properties of grass carp EpCAM (gcEpCAM) in a fish kidney cell line (CIK) via overexpression of gcEpCAM or gcEpCAM intracellular domain (gcEpICD) deletion mutant. Results showed that gcEpCAM overexpression significantly changed the cell morphology, and the proliferation of the cells transfected with gcEpCAM was significantly decreased when compared to the control cells, which is unexpectedly opposite to the increasing effects induced by its mammalian homolog. Moreover, overexpression of gcEpICD deletion mutant had no effect on cell proliferation, indicating gcEpICD's involvement in the cell growth control that is concerted with its role in mammalian model. Additionally, gcEpCAM overexpression increased cell migration which is at least partially consistent with the findings in mammalian cells in which EpCAM expression both positively and negatively affects cell migration. It is worth noting that gcEpICD was not essential to the stimulatory effect of gcEpCAM on cell migration, but overexpression of human EpICD in tumor cells increases cell migration, suggesting the functional discrepancy of EpICD in fish and mammals. In conclusion, we elucidated the cellular functionality of EpCAM in fish cells which will be of benefit to defining the functions of fish EpCAM and also provide rewarding information on the functional evolution of EpCAM in vertebrates.