Defects of mitochondrial function have long been suspected to contribute to the development and progression of cancer. Mitochondria besides their roles as powerhouses and biosynthetic hubs are a main source of ROS. Indeed, the maintenance of the mitochondrial potential by means of electron transfer chain (ETC) during respiration produces superoxide as a main byproduct. In cancer cells, it has been reported that natural occurrence of mutations partially impairing ETC complex I and identification of an unprecedented phenotype corresponding to TCA cycle overload promote mtROS-dependent tumor metastasis. In this context, we recently found that several chemotherapies, including doxorubicin and cisplatin, promote ROS production and ROS-induced breast cancer cell migration and metastasis. On the other hand, in another tumor type, we also found that radiotherapy increases cancer cell respiration and promotes a morphological change evoking an epithelial-to-mesenchymal transition (EMT). Here, we will thus investigate whether X-ray radiotherapy promote breast cancer cell EMT, migration, invasion and metastasis.
This project will increase the understanding how radiotherapy promotes the metastatic potential of cancer cells and how mitochondria-targeted anti-oxidants or other metabolic targets might reverse this phenotype.