EMID1: a multifunctional molecule identified in a murine model for the invasion- independent metastasis pathway

Our previous analysis using a mouse metastasis model identified EMI Domain Containing 1 (EMID1) as a potential candidate metastasis-promoting gene. Although EMID1 was isolated as a member of the Emu gene family, which is expressed during mouse embryogenesis, little is known about the molecule. We sought to clarify the molecular function of EMID1 and the protein expression. Overexpression and knockdown studies using mouse cell lines identified two novel functions of EMID1: intracellular signaling involving enhancement of cell growth via cell cycle promotion and suppression of cell motility, and inhibition of cell-matrix adhesion by extracellularly secreted EMID1. EMID1 deposited on the culture dish induced self-detachment of cells that overexpressed the protein and inhibited adhesion of additionally seeded cells. This multifunctional property involving both intracellular signaling and the extracellular matrix suggests that EMID1 may be a matricellular proteins. Expression analysis using immunohistochemical staining revealed expression of EMID1 that was limited to chief cells of the gastric fundic gland and β cells of the pancreatic islets in normal adult human tissues, implying cell-specific functions of this molecule. In addition, increased expression of EMID1 protein detected in some cases of human cancers implies that EMID1 might be a new therapeutic target for cancer treatment.