ArticleBMC cancer2020
The Axin2-snail axis promotes bone invasion by activating cancer-associated fibroblasts in oral squamous cell carcinoma.
Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Stromal cells contribute to progression, recurrence, and metastasis in oral squamous cell carcinoma: a call for therapy.Journal of translational medicine · 2026Review
- Inhibition of CXCR4 suppresses bone invasion in a murine model of oral squamous cell carcinoma.BMC oral health · 2025Article
- Article
- Desmoplastic reaction in the microenvironment of head and neck and other solid tumors: the therapeutic barrier.Therapeutic advances in medical oncology · 2025Review
- Chemokines and their receptors in oral squamous cell carcinoma: mechanisms, clinical significance, and therapeutic implications.Frontiers in immunology · 2025Review
- Cancer associated fibroblasts and metabolic reprogramming: unraveling the intricate crosstalk in tumor evolution.Journal of hematology & oncology · 2024Review
- Article
- Investigation of bone invasion and underlying mechanisms of oral cancer using a cell line-derived xenograft model.Oncology letters · 2022Article
- Crosstalk between cancer and different cancer stroma subtypes promotes the infiltration of tumor‑associated macrophages into the tumor microenvironment of oral squamous cell carcinoma.International journal of oncology · 2022Article
- Significance of cancer stroma for bone destruction in oral squamous cell carcinoma using different cancer stroma subtypes.Oncology reports · 2022Article
- Risk Factors of Microscopically Tumor-Free Surgical Margins for Recurrence and Survival of Oral Squamous Cell Carcinoma Patients.Frontiers in oncology · 2022Article
- Cancer-associated fibroblasts: overview, progress, challenges, and directions.Cancer gene therapy · 2021Review
- Stromal cells in the tumor microenvironment promote the progression of oral squamous cell carcinoma.International journal of oncology · 2021Article
- Platelet CLEC2-Podoplanin Axis as a Promising Target for Oral Cancer Treatment.Frontiers in immunology · 2021Review
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIn bone-invasive oral squamous cell carcinoma (OSCC), cancer-associated fibroblasts (CAFs) infiltrate into bony tissue ahead of OSCC cells. In the present study, we aimed to investigate the role of the Axin2-Snail axis in the biological behaviour of CAFs and bone invasion in OSCC.
methodsThe clinicopathological significance of Axin2 and Snail expression was investigated by immunohistochemistry in an OSCC cohort containing 217 tissue samples from patients with long-term follow-up. The influence of the Axin2-Snail axis on the biological behaviour of OSCC cells and CAFs was further investigated both in vitro and in vivo.
resultsAxin2 expression was significantly associated with Snail expression, the desmoplasia status, and bone invasion in patients with OSCC. In multivariate analysis, lymph node metastasis, desmoplasia, Axin2 expression, and Snail expression were independent poor prognostic factors in our cohort. Consistent with these findings, OSCC cells demonstrated attenuated oncogenic activity as well as decreased expression of Snail and various cytokines after Axin2 knockdown in vitro. Among the related cytokines, C-C motif chemokine ligand 5 (CCL5) and interleukin 8 (IL8) demonstrated a strong influence on the biological behaviour of CAFs in vitro. Moreover, both the desmoplastic reaction and osteolytic lesions in the calvaria were predominantly decreased after Axin2 knockdown in OSCC cells in vivo using a BALB/c athymic nude mouse xenograft model.
conclusionsOncogenic activities of the Axin2-Snail axis are not limited to the cancer cells themselves but rather extend to CAFs via regulation of the cytokine-mediated cancer-stromal interaction, with further implications for bone invasion as well as a poor prognosis in OSCC.
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