ArticleMolecular carcinogenesis2019
Wnt signaling dynamics in head and neck squamous cell cancer tumor-stroma interactions.
Article in Molecular carcinogenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 68 citations in OpenAlex.
- Lgr6Genes & diseases · 2026Review
- Cancer-associated fibroblasts in head and neck tumours: signalling networks and therapeutic implications with insights from vestibular schwannoma.Frontiers in cell and developmental biology · 2026Review
- Improved Methods for the Stable Generation of Human Papillomavirus-Driven Head and Neck Cancer Cell Lines.Molecular carcinogenesis · 2025Article
- Revisiting Curcumin in Cancer Therapy: Recent Insights into Molecular Mechanisms, Nanoformulations, and Synergistic Combinations.Current issues in molecular biology · 2025Review
- Interplay between tunneling nanotubes and Wnt Signaling: Insights into cytoskeletal regulation and therapeutic potential.Biochemistry and biophysics reports · 2025Review
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Advances in the development of Wnt/β-catenin signaling inhibitors.RSC medicinal chemistry · 2025Review
- Phytochemicals and their Nanoformulations for Overcoming Drug Resistance in Head and Neck Squamous Cell Carcinoma.Pharmaceutical research · 2025Review
- CAF-mediated regulation of prostate cancer stem cell stemness via the Wnt/β-catenin and SDF-1/CXCR4 pathways in castration-resistant prostate cancer.Frontiers in cell and developmental biology · 2025Article
- Mechanistic studies ofFrontiers in oncology · 2025Article
- M6A-mediated molecular patterns and tumor microenvironment infiltration characterization in nasopharyngeal carcinoma.Cancer biology & therapy · 2024Article
- A bioengineered tumor matrix-based scaffold for the evaluation of melatonin efficacy on head and neck squamous cancer stem cells.Materials today. Bio · 2024Article
- Reduced Proline-Rich Tyrosine Kinase 2 Promotes Tumor Metastasis by Activating Epithelial-Mesenchymal Transition in Colorectal Cancer.Digestive diseases and sciences · 2024Article
- Anti-tumor efficacy ofWorld journal of gastroenterology · 2024Article
- Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.Acta pharmacologica Sinica · 2024Review
- Crosstalk between CAFs and tumour cells in head and neck cancer.Cell death discovery · 2024Review
- Long noncoding RNA H19: functions and mechanisms in regulating programmed cell death in cancer.Cell death discovery · 2024Review
- Cancer-associated fibroblast cell surface markers as potential biomarkers or therapeutic targets in lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Wnt/β-catenin signaling pathway: an attractive potential therapeutic target in osteosarcoma.Frontiers in oncology · 2024Review
- Navigating Tumour Microenvironment and Wnt Signalling Crosstalk: Implications for Advanced Cancer Therapeutics.Cancers · 2023Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Wnt pathway activation maintains the cancer stem cell (CSC) phenotype and promotes tumor progression, making it an attractive target for anti-cancer therapy. Wnt signaling at the tumor and tumor microenvironment (TME) front have not been investigated in depth in head and neck squamous cell carcinoma (HNSCC). In a cohort of 48 HNSCCs, increased Wnt signaling, including Wnt genes (AXIN2, LGR6, WISP1) and stem cell factors (RET, SOX5, KIT), were associated with a more advanced clinical stage. Key Wnt pathway proteins were most abundant at the cancer epithelial-stromal boundary. To investigate these observations, we generated three pairs of cancer-cancer associated fibroblast (CAF) cell lines derived from the same HNSCC patients. 3D co-culture of cancer spheres and CAFs mimicked these in vivo interactions, and using these we observed increased expression of Wnt genes (eg, WNT3A, WNT7A, WNT16) in both compartments. Of these Wnt ligands, we found Wnt3a, and less consistently Wnt16, activated Wnt signaling in both cancer cells and CAFs. Wnt activation increased CSC characteristics like sphere formation and invasiveness, which was further regulated by the presence of CAFs. Time lapse microscopy also revealed preferential Wnt activation of cancer cells. Wnt inhibitors, OMP-18R5 and OMP-54F28, significantly reduced growth of HNSCC patient-derived xenografts and suppressed Wnt activation at the tumor epithelial-stromal boundary. Taken together, our findings suggest that Wnt signaling is initiated in cancer cells which then activate CAFs, and in turn perpetuate a paracrine signaling loop. This suggests that targeting Wnt signaling in the TME is essential.
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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.