ArticleMolecular cancer2015
Dioxin receptor regulates aldehyde dehydrogenase to block melanoma tumorigenesis and metastasis.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Integrating machine learning and molecular dynamics simulation to decipher the molecular network of dioxin-associated liposarcoma.Scientific reports · 2025Article
- Aryl Hydrocarbon Receptor (AHR) Suppresses Arsenic (AsInternational journal of biological sciences · 2025Article
- Tumor-Suppressive Functions of the Aryl Hydrocarbon Receptor (AhR) and AhR as a Therapeutic Target in Cancer.Biology · 2023Review
- The Ah Receptor from Toxicity to Therapeutics: Report from the 5th AHR Meeting at Penn State University, USA, June 2022.International journal of molecular sciences · 2023Article
- From Nucleus to Organs: Insights of Aryl Hydrocarbon Receptor Molecular Mechanisms.International journal of molecular sciences · 2022Review
- Liver regeneration after partial hepatectomy is improved in the absence of aryl hydrocarbon receptor.Scientific reports · 2022Article
- Consideration of possible effects of vitamin D on established cancer, with reference to malignant melanoma.Pigment cell & melanoma research · 2022Review
- Aryl Hydrocarbon Receptor: From Homeostasis to Tumor Progression.Frontiers in cell and developmental biology · 2022Review
- CD29 targeted near-infrared photoimmunotherapy (NIR-PIT) in the treatment of a pigmented melanoma model.Oncoimmunology · 2022Article
- Converging Roles of the Aryl Hydrocarbon Receptor in Early Embryonic Development, Maintenance of Stemness, and Tissue Repair.Toxicological sciences : an official journal of the Society of Toxicology · 2021Review
- Effect of melanoma stem cells on melanoma metastasis.Oncology letters · 2021Review
- Identification of pathways modulating vemurafenib resistance in melanoma cells via a genome-wide CRISPR/Cas9 screen.G3 (Bethesda, Md.) · 2021Article
- AhR and Cancer: From Gene Profiling to Targeted Therapy.International journal of molecular sciences · 2021Review
- Diabetes mellitus type 2 drives metabolic reprogramming to promote pancreatic cancer growth.Gastroenterology report · 2020Article
- Sustained activation of the Aryl hydrocarbon Receptor transcription factor promotes resistance to BRAF-inhibitors in melanoma.Nature communications · 2018Article
- Cancer Stem Cell Vaccination With PD-L1 and CTLA-4 Blockades Enhances the Eradication of Melanoma Stem Cells in a Mouse Tumor Model.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2018Article
- Dioxin Receptor Adjusts Liver Regeneration After Acute Toxic Injury and Protects Against Liver Carcinogenesis.Scientific reports · 2017Article
- Salinomycin reduces stemness and induces apoptosis on human ovarian cancer stem cell.Journal of gynecologic oncology · 2017Article
- Therapeutic implications of cellular and molecular biology of cancer stem cells in melanoma.Molecular cancer · 2017Review
- IGF-1 contributes to the expansion of melanoma-initiating cells through an epithelial-mesenchymal transition process.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe dioxin (AhR) receptor can have oncogenic or tumor suppressor activities depending on the phenotype of the target cell. We have shown that AhR knockdown promotes melanoma primary tumorigenesis and lung metastasis in the mouse and that human metastatic melanomas had reduced AhR levels with respect to benign nevi.
methodsMouse melanoma B16F10 cells were engineered by retroviral transduction to stably downregulate AhR expression, Aldh1a1 expression or both. They were characterized for Aldh1a1 activity, stem cell markers and migration and invasion in vitro. Their tumorigenicity in vivo was analyzed using xenografts and lung metastasis assays as well as in vivo imaging.
resultsDepletion of aldehyde dehydrogenase 1a1 (Aldh1a1) impairs the pro-tumorigenic and pro-metastatic advantage of melanoma cells lacking AhR expression (sh-AhR). Thus, Aldh1a1 knockdown in sh-AhR cells (sh-AhR + sh-Aldh1a1) diminished their migration and invasion potentials and blocked tumor growth and metastasis to the lungs in immunocompetent AhR+/+ recipient mice. However, Aldh1a1 downmodulation in AhR-expressing B16F10 cells did not significantly affect tumor growth in vivo. Aldh1a1 knockdown reduced the high levels of CD133(+)/CD29(+)/CD44(+) cells, melanosphere size and the expression of the pluripotency marker Sox2 in sh-AhR cells. Interestingly, Sox2 increased Aldh1a1 expression in sh-AhR but not in sh-AhR + sh-Aldh1a1 cells, suggesting that Aldh1a1 and Sox2 may be co-regulated in melanoma cells. In vivo imaging revealed that mice inoculated with AhR + Aldh1a1 knockdown cells had reduced tumor burden and enhanced survival than those receiving Aldh1a1-expressing sh-AhR cells.
conclusionsAldh1a1 overactivation in an AhR-deficient background enhances melanoma progression. Since AhR may antagonize the protumoral effects of Aldh1a1, the AhR(low)-Aldh1a1(high) phenotype could be indicative of bad outcome in melanoma.
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