Irradiation-induced Cell Migration (ICM) Involves EMT and is Regulated by Caspases

Irradiation-induced cell migration (ICM) in Drosophila is a recently discovered process in our lab, in which irradiated epithelial cells compromised for caspase activity acquire potent migration and invasion capacities. During this process cells undergo dramatic morphological and anatomical changes, including loss of apico-basal polarity and cell delamination, ECM remodeling, Rho GTPases activation and formation of cellular protrusions, and eventually intra- and inter-tissue migration and invasion. This dramatic cellular remodeling is reminiscent of the epithelial-mesenchymal transition (EMT) process, which is important for organismal development and for cancer cell dissemination. To characterize these EMT-like aspects, we first carefully followed this cellular transition. We show that ICM involves extensive remodeling of the tissue ECM manifested by the degradation of the basement-membrane (BM). The vast majority of the migrating cells become untethered from the BM and delaminate basally breaking through the degraded BM. We then demonstrate that there are no directional migration paths, rather the cells migrate randomly and are scattered throughout the tissue. At the molecular level, we identified key regulators of developmental and pathological EMT as mediators of ICM. Importantly, we show that the EMT process during ICM is highly efficient, affecting most of the cells, and that caspases appear to be only involved in the attenuation of the subsequent migration process. Given the high resemblance between ICM and EMT, and the fact that the latter is believed to be involved in metastatic progression of tumor cells, our findings may provide new insights on the role of caspases as tumor suppressor genes.