A double-edged sword: role of apoptosis repressor with caspase recruitment domain (ARC) in tumorigenesis and ischaemia/reperfusion (I/R) injury

Apoptosis repressor with caspase recruitment domain (ARC) acts as a potent and multifunctional inhibitor of apoptosis, which is mainly expressed in postmitotic cells, including cardiomyocytes. ARC is special for its N-terminal caspase recruitment domain and caspase recruitment domain. Due to the powerful inhibition of apoptosis, ARC is mainly reported to act as a cardioprotective factor during ischaemia‒reperfusion (I/R) injury, preventing cardiomyocytes from being devastated by various catastrophes, including oxidative stress, calcium overload, and mitochondrial dysfunction in the circulatory system. However, recent studies have found that ARC also plays a potential regulatory role in tumorigenesis especially in colorectal cancer and renal cell carcinomas, through multiple apoptosis-associated pathways, which remains to be explored in further studies. Therefore, ARC regulates the body and maintains the balance of physiological activities with its interesting duplex. This review summarizes the current research progress of ARC in the field of tumorigenesis and ischaemia/reperfusion injury, to provide overall research status and new possibilities for researchers.