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PKCλ/ι Loss Induces Autophagy, Oxidative Phosphorylation, and NRF2 to Promote Liver Cancer Progression
- Source :
- Cancer Cell. 38:247-262.e11
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Oxidative stress plays a critical role in liver tissue damage and in hepatocellular carcinoma (HCC) initiation and progression. However, the mechanisms that regulate autophagy and metabolic reprogramming during reactive oxygen species (ROS) generation, and how ROS promote tumorigenesis, still need to be fully understood. We show that protein kinase C (PKC) λ/ι loss in hepatocytes promotes autophagy and oxidative phosphorylation. This results in ROS generation, which through NRF2 drives HCC through cell-autonomous and non-autonomous mechanisms. Although PKCλ/ι promotes tumorigenesis in oncogene-driven cancer models, emerging evidence demonstrate that it is a tumor suppressor in more complex carcinogenic processes. Consistently, PKCλ/ι levels negatively correlate with HCC histological tumor grade, establishing this kinase as a tumor suppressor in liver cancer.
- Subjects :
- 0301 basic medicine
Cancer Research
Carcinoma, Hepatocellular
NF-E2-Related Factor 2
medicine.disease_cause
Oxidative Phosphorylation
Cell Line
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Autophagy
medicine
Animals
Humans
Protein Kinase C
Protein kinase C
Mice, Knockout
chemistry.chemical_classification
Reactive oxygen species
Kinase
Liver Neoplasms
Cancer
Hep G2 Cells
Cell Biology
medicine.disease
Isoenzymes
HEK293 Cells
030104 developmental biology
Oncology
chemistry
030220 oncology & carcinogenesis
Disease Progression
Cancer research
RNA Interference
Carcinogenesis
Liver cancer
Oxidative stress
Subjects
Details
- ISSN :
- 15356108
- Volume :
- 38
- Database :
- OpenAIRE
- Journal :
- Cancer Cell
- Accession number :
- edsair.doi.dedup.....3564b693b42ac3915532746cf974a0e4
- Full Text :
- https://doi.org/10.1016/j.ccell.2020.05.018