Phosphorylated Nuclear Receptor Nur77 Protects Melanoma Cells From Glucose Starvation-induced Cell Death

Orphan nuclear receptor Nur77 is translated by an immediate-early gene encoded by NR4A1.At the same time,it’s a transcription factor.Nur77 participates in various fundamental cellular processes such as growth,proliferation,differentiation,migration and apoptosis through several mechanisms,including:(i)via a transcriptional dependent pathway;(ii)interaction with various proteins;(iii)subcellular localization and others.In our study,we newly discover a novel function of Nur77 in melanoma cells.In the absence of glucose,ERK2 is activated and phosphorylate Nur77.Phosphorylated Nur77 transferred to mitochondria.And then,Nur77 help to maintain NADPH and GSH levels and eliminate ROS to protect cells from glucose deprivation-induced cell death.We further demonstrated in vivo that Nur77 contributes to the survival of circulating tumor cells in peripheral blood and further promotes tumor cell metastasis.In conclusion,this study demonstrates that Nur77 plays a positive role in melanoma cells when they are responded to metabolic stress.