Nrf2-p62 autophagy pathway and its response to oxidative stress in hepatocellular carcinoma

Desirée Bartolini, Katiuscia Dallaglio, Pierangelo Torquato, Marta Piroddi, Francesco Galli

Research output: Contribution to journalReview article

22 Citations (Scopus)

Abstract

Deregulation of autophagy is proposed to play a key pathogenic role in hepatocellular carcinoma (HCC), the most common primary malignancy of the liver and the third leading cause of cancer death. Autophagy is an evolutionarily conserved catabolic process activated to degrade and recycle cell's components. Under stress conditions, such as oxidative stress and nutrient deprivation, autophagy is an essential survival pathway that operates in harmony with other stress response pathways. These include the redox-sensitive transcription complex Nrf2-Keap1 that controls groups of genes with roles in detoxification and antioxidant processes, intermediary metabolism, and cell cycle regulation. Recently, a functional association between a dysfunctional autophagy and Nrf2 pathway activation has been identified in HCC. This appears to occur through the physical interaction of the autophagy adaptor p62 with the Nrf2 inhibitor Keap1, thus leading to increased stabilization and transcriptional activity of Nrf2, a key event in reprogramming metabolic and stress response pathways of proliferating hepatocarcinoma cells. These emerging molecular mechanisms and the therapeutic perspective of targeting Nrf2-p62 interaction in HCC are discussed in this paper along with the prognostic value of autophagy in this type of cancer.

Original languageEnglish
Pages (from-to)54-71
Number of pages18
JournalTranslational Research
Volume193
DOIs
Publication statusPublished - Mar 1 2018

Fingerprint

Detoxification
Oxidative stress
Deregulation
Autophagy
Transcription
Metabolism
Liver
Nutrients
Hepatocellular Carcinoma
Oxidative Stress
Stabilization
Antioxidants
Genes
Chemical activation
Cells
Association reactions
Neoplasms
Physiological Stress
Cellular Structures
Oxidation-Reduction

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Biochemistry, medical

Cite this

Nrf2-p62 autophagy pathway and its response to oxidative stress in hepatocellular carcinoma. / Bartolini, Desirée; Dallaglio, Katiuscia; Torquato, Pierangelo; Piroddi, Marta; Galli, Francesco.

In: Translational Research, Vol. 193, 01.03.2018, p. 54-71.

Research output: Contribution to journalReview article

Bartolini, Desirée ; Dallaglio, Katiuscia ; Torquato, Pierangelo ; Piroddi, Marta ; Galli, Francesco. / Nrf2-p62 autophagy pathway and its response to oxidative stress in hepatocellular carcinoma. In: Translational Research. 2018 ; Vol. 193. pp. 54-71.
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