Comparative subcellular localization of NRF2 and KEAP1 during the hepatocellular carcinoma development in vivo
Por:
Guerrero-Escalera, Dafne, Alarcón-Sánchez B.R., Arellanes-Robledo, Jaime, Cruz-Rangel, Armando, del Pozo-Yauner, Luis, Chagoya de Sanchez, Victoria, Resendis-Antonio, Osbaldo, Villa-Trevino, Saul, Torres-Mena J.E., Pérez-Carreón J.I.
Publicada:
1 may 2022
Resumen:
The activation of Nuclear Factor, Erythroid 2 Like 2 - Kelch Like ECH
Associated Protein 1 (NRF2-KEAP1) signaling pathway plays a critical
dual role by either protecting or promoting the carcinogenesis process.
However, its activation or nuclear translocation during hepatocellular
carcinoma (HCC) progression has not been addressed yet. This study
characterizes the subcellular localization of both NRF2 and KEAP1 during
diethylnitrosamine-induced hepatocarcinogenesis in the rat. NRF2-KEAP1
pathway was continuously activated along with the increased expression
of its target genes, namely Nqo1, Hmox1, Gclc, and Ptgr1. Similarly, the
nuclear translocation of NRF2, MAF, and KEAP1 increased in HCC cells
from weeks 12 to 22 during HCC progression. Likewise, colocalization of
NRF2 with KEAP1 was higher in the cell nuclei of HCC neoplastic nodules
than in surrounding cells. Moreover, immunofluorescence analyses
revealed that the interaction of KEAP1 with filamentous Actin was
disrupted in HCC cells. This disruption may be contributing to the
release and nuclear translocation of NRF2 since the cortical actin
cytoskeleton serves as anchoring of KEAP1. In conclusion, this evidence
indicates that NRF2 is progressively activated and promotes the
progression of experimental HCC.
Filiaciones:
Laboratory of Liver Diseases, National Institute of Genomic Medicine, CDMX, Mexico
Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute, CDMX, Mexico
Directorate of Cátedras, National Council of Science and Technology, CDMX, Mexico
Department of Pathology, College of Medicine, University of South AlabamaAL, United States
Institute of Cellular Physiology, National Autonomous University of Mexico, CDMX, Mexico
Natl Inst Genom Med, Lab Liver Dis, Cdmx, Mexico
Natl Polytech Inst, Ctr Res & Adv Studies, Dept Cell Biol, Cdmx, Mexico
Natl Council Sci & Technol, Directorate Catedras, Cdmx, Mexico
Univ S Alabama, Coll Med, Dept Pathol, Mobile, AL USA
Univ Nacl Autonoma Mexico, Inst Cellular Physiol, Cdmx, Mexico
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