| First Author | Li T | Year | 2020 |
| Journal | Front Cell Dev Biol | Volume | 8 |
| Pages | 225 | PubMed ID | 32363190 |
| Mgi Jnum | J:292661 | Mgi Id | MGI:6436071 |
| Doi | 10.3389/fcell.2020.00225 | Citation | Li T, et al. (2020) Defects in mTORC1 Network and mTORC1-STAT3 Pathway Crosstalk Contributes to Non-inflammatory Hepatocellular Carcinoma. Front Cell Dev Biol 8:225 |
| abstractText | Background and Aims: Mammalian target of rapamycin complex 1 (mTORC1) is frequently hyperactivated in hepatocellular carcinoma (HCC). Cases of HCC without inflammation and cirrhosis are not rarely seen in clinics. However, the molecular basis of non-inflammatory HCC remains unclear. Methods: Spontaneous non-inflammatory HCC in mice was triggered by constitutive elevation of mTORC1 by liver-specific TSC1 knockout (LTsc1KO). A multi-omics approach was utilized on tumor tissues to better understand the molecular basis for the development of HCC in the LTsc1KO model. Results: We showed that LTsc1KO in mice triggered spontaneous non-inflammatory HCC, with molecular characteristics similar to those of diethylnitrosamine-mediated non-cirrhotic HCC. Mitochondrial and autophagy defects, as well as hepatic metabolic disorder were manifested in HCC development by LTsc1KO. mTORC1 activation on its own regulated an oncogenic network (DNA-damage-inducible transcript 4, nuclear protein 1, and fibroblast growth factor 21), and mTORC1-signal transducer and activator of transcription pathway crosstalk that altered specific metabolic pathways contributed to the development of non-inflammatory HCC. Conclusion: Our findings reveal the mechanisms of mTORC1-driven non-inflammatory HCC and provide insight into further development of a protective strategy against non-inflammatory HCC. |
