Modulation of c-Met signaling and cellular sensitivity to radiation: potential implications for therapy.

Abstract

The c-Met/hepatocyte growth factor receptor and its family members are known to promote cancer cell migration and invasion. Signaling within and beyond this pathway contributes to the systemic spread of metastases through induction of the epithelial-mesenchymal transition, a process also implicated in mediating resistance to current anticancer therapies, including radiation. Induction of c-Met has also been observed after irradiation, suggesting that c-Met participates in radiation-induced disease progression through the epithelial-mesenchymal transition. Therefore, c-Met inhibition is an attractive target for potentially mitigating radiation resistance. This article summarizes key findings regarding crosstalk between radiotherapy and c-Met and discusses studies performed to date in which c-Met inhibition was used as a strategy to increase cellular radiosensitivity.