Metabolic Regulation Of Pluripotent Stem Cells And Cancer Cells

Metabolic remodelling has emerged as critical for stem cell pluripotency,however,the underlying mechanisms have yet to be fully elucidated.Here,we found that the glycine cleavage system(GCS)is highly activated to promote stem cell pluripotency and during somatic cell reprogramming.Mechanistically,we revealed that the expression of Gldc,a rate-limiting GCS enzyme regulated by Sox2 and Lin28A,facilitates this activation.We further found that the activated GCS catabolizes glycine to fuel one-carbon units.Moreover,the activated GCS helps to cleave excess glycine and prevents methylglyoxal accumulation.Collectively,our results demonstrate a novel mechanism whereby GCS activation controls stem cell fate.Cancer progression depends on cellular metabolic reprogramming as both direct and indirect consequence of oncogenic lesions;however,the underlying mechanisms are still poorly understood.Here,we report that CUEDC2(CUE domain-containing protein 2)plays a vital role in facilitating aerobic glycolysis,or Warburg effect,in cancer cells.Mechanistically,we show that CUEDC2 upregulates the two key glycolytic proteins GLUT3 and LDHA via interacting with the glucocorticoid receptor(GR)or 14-3-3f,respectively.We further demonstrate that enhanced aerobic glycolysis is essential for the role of CUEDC2 to drive cancer progression.Moreover,using tissue microarray analysis,we show a correlation between the aberrant expression of CUEDC2,and GLUT3 and LDHA in clinical HCC samples,further demonstrating a link between CUEDC2 and the Warburg effect during cancer development.Taken together,our findings reveal a previously unappreciated function of CUEDC2 in cancer cell metabolism and tumorigenesis,illustrating how close oncogenic lesions are intertwined with metabolic alterations promoting cancer progression.