ArticleAlcoholism, clinical and experimental research2014
Alcohol activates the hedgehog pathway and induces related procarcinogenic processes in the alcohol-preferring rat model of hepatocarcinogenesis.
Article in Alcoholism, clinical and experimental research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Phytochemicals as Potential Lead Molecules against Hepatocellular Carcinoma.Current medicinal chemistry · 2024Review
- Aging reduces liver resiliency by dysregulating Hedgehog signaling.Aging cell · 2022Article
- Alcohol drinking inhibits NOTCH-PAX9 signaling in esophageal squamous epithelial cells.The Journal of pathology · 2021Article
- Review
- Integrative analysis of differential circular RNA and long non-coding RNA profiles and associated competing endogenous RNA networks in esophageal squamous cell carcinoma.Functional & integrative genomics · 2021Article
- The hedgehog pathway in nonalcoholic fatty liver disease.Critical reviews in biochemistry and molecular biology · 2018Review
- Hedgehog signalling in liver pathophysiology.Journal of hepatology · 2018Review
- Review
- Alcohol Reduces Arterial Remodeling by Inhibiting Sonic Hedgehog-Stimulated Stem Cell Antigen-1 Positive Progenitor Stem Cell Expansion.Alcoholism, clinical and experimental research · 2017Article
- Review
- Implication of the Hedgehog pathway in hepatocellular carcinoma.World journal of gastroenterology · 2017Review
- Ductular reaction-on-a-chip: Microfluidic co-cultures to study stem cell fate selection during liver injury.Scientific reports · 2016Article
- Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features.International journal of oncology · 2016Article
- Alcoholic Beverage Consumption and Chronic Diseases.International journal of environmental research and public health · 2016Review
- Article
- Lipids and Oxidative Stress Associated with Ethanol-Induced Neurological Damage.Oxidative medicine and cellular longevity · 2016Review
- Curcumin regulates cell fate and metabolism by inhibiting hedgehog signaling in hepatic stellate cells.Laboratory investigation; a journal of technical methods and pathology · 2015Article
- Molecular mechanisms of ethanol-associated oro-esophageal squamous cell carcinoma.Cancer letters · 2015Review
- Hedgehog signaling and steroidogenesis.Annual review of physiology · 2015Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundAlcohol consumption promotes hepatocellular carcinoma (HCC). The responsible mechanisms are not well understood. Hepatocarcinogenesis increases with age and is enhanced by factors that impose a demand for liver regeneration. Because alcohol is hepatotoxic, habitual alcohol ingestion evokes a recurrent demand for hepatic regeneration. The alcohol-preferring (P) rat model mimics the level of alcohol consumption by humans who habitually abuse alcohol. Previously, we showed that habitual heavy alcohol ingestion amplified age-related hepatocarcinogenesis in P rats, with over 80% of alcohol-consuming P rats developing HCCs after 18 months of alcohol exposure, compared with only 5% of water-drinking controls.
methodsHerein, we used quantitative real-time PCR and quantitative immunocytochemistry to compare liver tissues from alcohol-consuming P rats and water-fed P rat controls after 6, 12, or 18 months of drinking. We aimed to identify potential mechanisms that might underlie the differences in liver cancer formation and hypothesized that chronic alcohol ingestion would activate Hedgehog (HH), a regenerative signaling pathway that is overactivated in HCC.
resultsChronic alcohol ingestion amplified age-related degenerative changes in hepatocytes, but did not cause appreciable liver inflammation or fibrosis even after 18 months of heavy drinking. HH signaling was also enhanced by alcohol exposure, as evidenced by increased levels of mRNAs encoding HH ligands, HH-regulated transcription factors, and HH target genes. Immunocytochemistry confirmed increased alcohol-related accumulation of HH ligand-producing cells and HH-responsive target cells. HH-related regenerative responses were also induced in alcohol-exposed rats. Three of these processes (i.e., deregulated progenitor expansion, the reverse Warburg effect, and epithelial-to-mesenchymal transitions) are known to promote cancer growth in other tissues.
conclusionsAlcohol-related changes in Hedgehog signaling and resultant deregulation of liver cell replacement might promote hepatocarcinogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.