Redox regulation in tumor cell epithelial-mesenchymal transition:molecular basis and therapeutic strategy

Epithelial–mesenchymal transition(EMT)is recognized as a driving force of cancer cell metastasis and drug resistance,two leading causes of cancer recurrence and cancer-related death.It is,therefore,logical in cancer therapy to target the EMT switch to prevent such cancer metastasis and recurrence.Previous reports have indicated that growth factors(such as epidermal growth factor and fibroblast growth factor)and cytokines(such as the transforming growth factor beta(TGF-β)family)are major stimulators of EMT.However,the mechanisms underlying EMT initiation and progression remain unclear.Recently,emerging evidence has suggested that reactive oxygen species(ROS),important cellular secondary messengers involved in diverse biological events in cancer cells,play essential roles in the EMT process in cancer cells by regulating extracellular matrix(ECM)remodeling,cytoskeleton remodeling,cell–cell junctions,and cell mobility.Thus,targeting EMT by manipulating the intracellular redox status may hold promise for cancer therapy.Herein,we will address recent advances in redox biology involved in the EMT process in cancer cells,which will contribute to the development of novel therapeutic strategies by targeting redox-regulated EMT for cancer treatment.