| First Author | Kudo Y | Year | 2020 |
| Journal | Cancer Cell | Volume | 38 |
| Issue | 2 | Pages | 247-262.e11 |
| PubMed ID | 32589943 | Mgi Jnum | J:296308 |
| Mgi Id | MGI:6466835 | Doi | 10.1016/j.ccell.2020.05.018 |
| Citation | Kudo Y, et al. (2020) PKClambda/iota Loss Induces Autophagy, Oxidative Phosphorylation, and NRF2 to Promote Liver Cancer Progression. Cancer Cell 38(2):247-262.e11 |
| abstractText | 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) lambda/iota 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 PKClambda/iota promotes tumorigenesis in oncogene-driven cancer models, emerging evidence demonstrate that it is a tumor suppressor in more complex carcinogenic processes. Consistently, PKClambda/iota levels negatively correlate with HCC histological tumor grade, establishing this kinase as a tumor suppressor in liver cancer. |
