SILENCING MICAL2 REPRESSES HUMAN CANCER CELL GROWTH AND INVASION INDUCING MESENCHYMAL TO EPITHELIAL TRANSITION

MICAL (Molecules Interacting with CasL)2 belongs to an evolutionarily conserved family of proteins that catalyze actin oxidation-reduction reactions destabilizing F-actin in cytoskeletal dynamics. Here we show for the first time that MICAL2 mRNA is significantly over-expressed in aggressive, poorly differentiated/ undifferentiated, primary gastric and renal human epithelial cancers. Immunohistochemistry showed MICAL2- positive cells on the cancer invasive front and in metastasizing cancer cells inside emboli, but not at sites of metastasis, suggesting MICAL2 expression was “on” in a subpopulation of primary cancer cells seemingly detaching from the tissue of origin, enter emboli and travel to distant sites, to be turned “off” once homing at the metastatic site occurred. In vitro, MICAL2 knock-down was clearly associated with induction of mesenchymal to epithelial transition, causing reduction of viability and loss of motility and invasion properties of human cancer cells. Moreover, expression of MICAL2 cDNA in MICAL2-depleted cells induced epithelial to mesenchymal transition. All together our data indicate MICAL2 over-expression is associated with cancer progression and metastatic disease. MICAL2 might be an important regulator of epithelial to mesenchymal transition and therefore a promising target for anti-metastatic therapy.