Molecular Mechanisms Regulating Obesity-Associated Hepatocellular Carcinoma.
HCC
NASH
epigenetic changes
genetic factors
obesity
therapeutics
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
20 May 2020
20 May 2020
Historique:
received:
30
04
2020
revised:
14
05
2020
accepted:
17
05
2020
entrez:
24
5
2020
pubmed:
24
5
2020
medline:
24
5
2020
Statut:
epublish
Résumé
Obesity is a global, intractable issue, altering inflammatory and stress response pathways, and promoting tissue adiposity and tumorigenesis. Visceral fat accumulation is correlated with primary tumor recurrence, poor prognosis and chemotherapeutic resistance. Accumulating evidence highlights a close association between obesity and an increased incidence of hepatocellular carcinoma (HCC). Obesity drives HCC, and obesity-associated tumorigenesis develops via nonalcoholic fatty liver (NAFL), progressing to nonalcoholic steatohepatitis (NASH) and ultimately to HCC. The better molecular elucidation and proteogenomic characterization of obesity-associated HCC might eventually open up potential therapeutic avenues. The mechanisms relating obesity and HCC are correlated with adipose tissue remodeling, alteration in the gut microbiome, genetic factors, ER stress, oxidative stress and epigenetic changes. During obesity-related hepatocarcinogenesis, adipokine secretion is dysregulated and the nuclear factor erythroid 2 related factor 1 (Nrf-1), nuclear factor kappa B (NF-κB), mammalian target of rapamycin (mTOR), phosphatidylinositol-3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways are activated. This review captures the present trends allied with the molecular mechanisms involved in obesity-associated hepatic tumorigenesis, showcasing next generation molecular therapeutic strategies and their mechanisms for the successful treatment of HCC.
Identifiants
pubmed: 32443737
pii: cancers12051290
doi: 10.3390/cancers12051290
pmc: PMC7281233
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : R01 CA230561
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA244993
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA240004
Pays : United States
Organisme : NIDDK NIH HHS
ID : 1R01DK107451-01A1
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107451
Pays : United States
Organisme : NCI NIH HHS
ID : 1R01CA230561-01A1, 1R01CA240004-01 and 1R01CA244993-01
Pays : United States
Organisme : U.S. Department of Defense
ID : CA170048
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