Emerging roles of ECSIT in immunity and tumorigenesis

Mitochondria are signaling hubs that produce immunomodulatory metabolites during the immune response. In addition, mitochondria also facilitate the recruitment and anchoring of immune signaling complexes during infection. Evolutionary conserved signaling intermediate in toll (ECSIT) was initially described as a positive regulator of the transcription factor Nuclear factor kappa-light chain enhancer of activated B cells (NF-κB). More recently, ECSIT has emerged as a regulator of bacterial clearance, mitochondrial reactive oxygen species (mROS), and mitophagy. In addition, ECSIT has been identified as a control point in responding to viral infection and tumorigenesis. Notably, ECSIT loss in different models and cell types has been found to lead to enhanced tumorigenesis. Thus, ECSIT functions as a metabolic tumor suppressor and limits cancer pathogenesis. In this review, we highlight the key functions and crosstalk mechanisms that ECSIT bridges between cell metabolism and immunity and focus then on the antitumor role of ECSIT independent of immunity.