ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Alcohol reshapes a liver premetastatic niche for cancer by extra- and intrahepatic crosstalk-mediated immune evasion.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- From steatosis to metastasis: microenvironmental reprogramming of the liver in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Targeting EZH2-driven cholesterol metabolic vulnerability through Napabucasin suppresses ovarian cancer metastasis.Cell death & disease · 2026Article
- IL-6 trans-Signaling Regulates Neutrophilic Inflammation in Alcohol-Associated Hepatitis.The American journal of pathology · 2026Article
- Mechanistic insights into hepatic metastasis of pancreatic cancer: molecular perspectives.Translational gastroenterology and hepatology · 2026Review
- Article
- Hydroxysafflower yellow A alleviates the inflammatory response in astrocytes following cerebral ischemia by inhibiting the LCN2/STAT3 feedback loop.Metabolic brain disease · 2025Article
- Regulation of metastatic organotropism.Trends in cancer · 2025Review
- Review
- Metastatic tumor growth in steatotic liver is promoted by HAS2-mediated fibrotic tumor microenvironment.The Journal of clinical investigation · 2025Article
- Inflammation and Immunity in Liver Neoplasms: Implications for Future Therapeutic Strategies.Molecular cancer therapeutics · 2025Review
- Luteolin improves precancerous conditions of the gastric mucosa by binding STAT3 and inhibiting LCN2 expression.International journal of biological sciences · 2025Article
- Mechanisms and therapeutic prospect of the JAK-STAT signaling pathway in liver cancer.Molecular and cellular biochemistry · 2025Review
- Lipocalin-2 and intestinal diseases.World journal of gastroenterology · 2024Review
- Immune dynamics shaping pre-metastatic and metastatic niches in liver metastases: from molecular mechanisms to therapeutic strategies.Molecular cancer · 2024Review
- Pre-metastatic niche: formation, characteristics and therapeutic implication.Signal transduction and targeted therapy · 2024Review
- Complex role of neutrophils in the tumor microenvironment: an avenue for novel immunotherapies.Cancer biology & medicine · 2024Review
- Unveiling the cancer risk nexus of the steatotic liver.Trends in endocrinology and metabolism: TEM · 2024Review
- Humanistic Health Management and Cancer: Associations of Psychology, Nutrition, and Exercise with Cancer Progression and Pathogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer metastatic organotropism is still a mystery. The liver is known to be susceptible to cancer metastasis and alcoholic injury. However, it is unclear whether and how alcohol facilitates liver metastasis and how to intervene. Here, we show that alcohol preferentially promotes liver metastasis in colon-cancer-bearing mice and post-surgery pancreatic cancer patients. The mechanism is that alcohol triggers an extra- and intrahepatic crosstalk to reshape an immunosuppressive liver microenvironment. In detail, alcohol upregulates extrahepatic IL-6 and hepatocellular IL-6 receptor expression, resulting in hepatocyte STAT3 signaling activation and downstream lipocalin-2 (Lcn2) upregulation. Furthermore, LCN2 promotes T cell-exhaustion neutrophil recruitment and cancer cell epithelial plasticity. In contrast, knocking out hepatocellular Stat3 or systemic Il6 in alcohol-treated mice preserves the liver microenvironment and suppresses liver metastasis. This mechanism is reflected in hepatocellular carcinoma patients, in that alcohol-associated signaling elevation in noncancerous liver tissue indicates adverse prognosis. Accordingly, we discover a novel application for BBI608, a small molecular STAT3 inhibitor that can prevent liver metastasis. BBI608 pretreatment protects the liver and suppresses alcohol-triggered premetastatic niche formation. In conclusion, under extra- and intrahepatic crosstalk, the alcoholic injured liver forms a favorable niche for cancer cell metastasis, while BBI608 is a promising anti-metastatic agent targeting such microenvironments.
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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.