PKCλ/ι Loss Induces Autophagy, Oxidative Phosphorylation, and NRF2 to Promote Liver Cancer Progression.
Animals
Autophagy
/ genetics
Carcinoma, Hepatocellular
/ genetics
Cell Line
Cell Line, Tumor
Disease Progression
HEK293 Cells
Hep G2 Cells
Humans
Isoenzymes
/ genetics
Liver Neoplasms
/ genetics
Mice, Knockout
NF-E2-Related Factor 2
/ genetics
Oxidative Phosphorylation
Protein Kinase C
/ genetics
RNA Interference
NRF2
PKCζ
PKCι
PKCλ
atypical PKC
autophagy
hepatocellular carcinoma
metabolic reprogramming
oxidative phosphorylation
reactive oxygen species
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
10 08 2020
10 08 2020
Historique:
received:
02
01
2020
revised:
31
03
2020
accepted:
21
05
2020
pubmed:
27
6
2020
medline:
9
3
2021
entrez:
27
6
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32589943
pii: S1535-6108(20)30268-3
doi: 10.1016/j.ccell.2020.05.018
pmc: PMC7423690
mid: NIHMS1599088
pii:
doi:
Substances chimiques
Isoenzymes
0
NF-E2-Related Factor 2
0
NFE2L2 protein, human
0
Protein Kinase C
EC 2.7.11.13
protein kinase C lambda
EC 2.7.11.13
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
247-262.e11Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK108743
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA218254
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA234245
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124308
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA211794
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA030199
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA023100
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG038072
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA234128
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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