PPAR Promotes Cancer Cell Glut1 Transcription Repression

Abundant nutrient availability including glucose and amino acids plays an important role in maintaining cancer cell energetic and biosynthetic pathways. As a nuclear receptor, peroxisome-proliferator-activated receptor (PPAR) regulates inflammation and cancer progression, however, it is still unclear the interaction of PPAR with the cancer cell glucose metabolism. Here we found that PPAR reduced Glut1 (Glucose transporter 1) protein and gene levels in HCT-116, SW480, HeLa, and MCF-7 cancer cell lines. In contrast, silenced PPAR reversed this event. Further analysis shows that PPAR directly targeted the consensus PPRE motif of Glut1 promoter region resulting in Glut1 transcription repression. PPAR-mediated Glut1 transcription repression led to decreased influx of glucose in cancer cells. These findings revealed a novel mechanism of PPAR-mediated cancer cell Glut1 transcription repression. J. Cell. Biochem. 118: 1556-1562, 2017. (C) 2016 Wiley Periodicals, Inc.