ArticleMolecular cancer2016
ErbB2 and p38γ MAPK mediate alcohol-induced increase in breast cancer stem cells and metastasis.
Article in Molecular cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
- ZWINT down-regulated by miR-495-3p inhibited lung metastasis of breast cancer by blocking p38 MAPK signaling pathway activation.Human cell · 2025Article
- Mapping Knowledge Landscapes and Themes Trends of Breast Cancer Stem Cells: A Comprehensive Data-Mining-Based Study.Annals of surgical oncology · 2025Article
- ALDH2 dysfunction and alcohol cooperate in cancer stem cell enrichment.Carcinogenesis · 2024Article
- Pirfenidone ameliorates alcohol-induced promotion of breast cancer in mice.Frontiers in oncology · 2024Article
- Review
- Adolescent- and adult-initiated alcohol exposure in mice differentially promotes tumorigenesis and metastasis of breast cancer.Alcohol, clinical & experimental research · 2023Article
- Alcohol and breast cancer.Pharmacological reports : PR · 2023Review
- Chronic Alcohol Exposure Promotes Cancer Stemness and Glycolysis in Oral/Oropharyngeal Squamous Cell Carcinoma Cell Lines by Activating NFAT Signaling.International journal of molecular sciences · 2022Article
- Deletion of p38γ attenuates ethanol consumption- and acetaminophen-induced liver injury in mice through promoting Dlg1.Acta pharmacologica Sinica · 2022Article
- Role of p38 MAP kinase in cancer stem cells and metastasis.Oncogene · 2022Review
- Alcohol, Drinking Pattern, and Chronic Disease.Nutrients · 2022Review
- The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma.Cell death & disease · 2022Article
- Impact of intestinal dysbiosis on breast cancer metastasis and progression.Frontiers in oncology · 2022Review
- Global Increase in Breast Cancer Incidence: Risk Factors and Preventive Measures.BioMed research international · 2022Review
- Alcohol Metabolism Enriches Squamous Cell Carcinoma Cancer Stem Cells That Survive Oxidative Stress via Autophagy.Biomolecules · 2021Article
- miRNA-148a and miRNA-30c expressions as potential biomarkers in breast cancer patients.Biochemistry and biophysics reports · 2021Article
- Review
- Utilizing the Hippo pathway as a therapeutic target for combating endocrine-resistant breast cancer.Cancer cell international · 2021Review
- Genome-wide associations between alcohol consumption and blood DNA methylation: evidence from twin study.Epigenomics · 2021Article
- Phosphorylation regulates cullin-based ubiquitination in tumorigenesis.Acta pharmaceutica Sinica. B · 2021Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundBoth epidemiological and experimental studies suggest that excessive alcohol exposure increases the risk for breast cancer and enhances metastasis/recurrence. We have previously demonstrated that alcohol enhanced the migration/invasion of breast cancer cells and cancer cells overexpressing ErbB2/HER2 were more sensitive to alcohol exposure. However, the underlying mechanisms remain unclear. This study was designed to investigate the mechanisms underlying alcohol-enhanced aggressiveness of breast cancer. Cancer stem cells (CSCs) play a critical role in cancer metastasis and recurrence.
methodsWe evaluated the effect of chronic alcohol exposure on mammary tumor development/metastasis in MMTV-neu transgenic mice and investigated the cell signaling in response to alcohol exposure in breast cancer cells overexpressing ErbB2/HER2. RESULTS AND DISCUSSION: Chronic alcohol exposure increased breast cancer stem cell-like CSC population and enhanced the lung and colon metastasis in MMTV-neu transgenic mice. Alcohol exposure caused a drastic increase in CSC population and mammosphere formation in breast cancer cells overexpressing ErbB2/HER2. Alcohol exposure stimulated the phosphorylation of p38γ MAPK (p-p38γ) which was co-localized with phosphorylated ErbB2 and CSCs in the mammary tumor tissues. In vitro results confirmed that alcohol activated ErbB2/HER2 and selectively increased p-p38γ MAPK as well as the interaction between p38γ MAPK and its substrate, SAP97. However, alcohol did not affect the expression/phosphorylation of p38α/β MAPKs. In breast cancer cell lines, high expression of ErbB2 and p-p38γ MAPK was generally correlated with more CSC population. Blocking ErbB2 signaling abolished heregulin β1- and alcohol-stimulated p-p38γ MAPK and its association with SAP97. More importantly, p38γ MAPK siRNA significantly inhibited an alcohol-induced increase in CSC population, mammosphere formation and migration/invasion of breast cancer cells overexpressing ErbB2.
conclusionsp38γ MAPK is downstream of ErbB2 and plays an important role in alcohol-enhanced aggressiveness of breast cancer. Therefore, in addition to ErbB2/HER2, p38γ MAPK may be a potential target for the treatment of alcohol-enhanced cancer aggressiveness.
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