PKCλ/ι Loss Induces Autophagy, Oxidative Phosphorylation, and NRF2 to Promote Liver Cancer Progression
| Autor: | Kudo, Yotaro, Sugimoto, Masayuki, Arias, Esperanza, Kasashima, Hiroaki, Cordes, Thekla, Linares, Juan F, Duran, Angeles, Nakanishi, Yuki, Nakanishi, Naoko, L'Hermitte, Antoine, Campos, Alex, Senni, Nadia, Rooslid, Tarmo, Roberts, Lewis R, Cuervo, Ana Maria, Metallo, Christian M, Karin, Michael, Diaz-Meco, Maria T, Moscat, Jorge |
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| Rok vydání: | 2020 |
| Předmět: |
Liver Cancer
autophagy NF-E2-Related Factor 2 Knockout Chronic Liver Disease and Cirrhosis Oncology and Carcinogenesis oxidative phosphorylation Cell Line NRF2 Mice Rare Diseases Animals Humans metabolic reprogramming 2.1 Biological and endogenous factors Oncology & Carcinogenesis Aetiology Protein Kinase C Cancer PKCζ reactive oxygen species Tumor Liver Disease Carcinoma Liver Neoplasms Neurosciences Hepatocellular Hep G2 Cells hepatocellular carcinoma PKCλ PKCι Isoenzymes HEK293 Cells atypical PKC Disease Progression RNA Interference Digestive Diseases |
| Zdroj: | Cancer cell, vol 38, iss 2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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