| First Author | Serna R | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 6 | Pages | 104325 |
| PubMed ID | 35601917 | Mgi Jnum | J:325003 |
| Mgi Id | MGI:7283693 | Doi | 10.1016/j.isci.2022.104325 |
| Citation | Serna R, et al. (2022) c-JUN inhibits mTORC2 and glucose uptake to promote self-renewal and obesity. iScience 25(6):104325 |
| abstractText | Metabolic syndrome is associated with obesity, insulin resistance, and the risk of cancer. We tested whether oncogenic transcription factor c-JUN metabolically reprogrammed cells to induce obesity and cancer by reduction of glucose uptake, with promotion of the stemness phenotype leading to malignant transformation. Liquid alcohol, high-cholesterol, fat diet (HCFD), and isocaloric dextrin were fed to wild-type or experimental mice for 12 months to promote hepatocellular carcinoma (HCC). We demonstrated 40% of mice developed liver tumors after chronic HCFD feeding. Disruption of liver-specific c-Jun reduced tumor incidence 4-fold and improved insulin sensitivity. Overexpression of c-JUN downregulated RICTOR transcription, leading to inhibition of the mTORC2/AKT and glycolysis pathways. c-JUN inhibited GLUT1, 2, and 3 transactivation to suppress glucose uptake. Silencing of RICTOR or c-JUN overexpression promoted self-renewal ability. Taken together, c-JUN inhibited mTORC2 via RICTOR downregulation and inhibited glucose uptake via downregulation of glucose intake, leading to self-renewal and obesity. |
