ArticleFrontiers in pharmacology2022
Halofuginone inhibits tumor migration and invasion by affecting cancer-associated fibroblasts in oral squamous cell carcinoma.
Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 11 citations in OpenAlex.
- Emerging agents that target signaling pathways in cancer fibroblast cells (Review).International journal of oncology · 2026Review
- Stromal homeostasis-restoring "rocket-like" nanomedicine inhibited pancreatic tumor growth in vivo.Materials today. Bio · 2026Article
- Single-cell RNA sequencing identifies cancer-associated fibroblast marker genes for determining cancer subtypes in oral squamous cell carcinoma and predicting patient prognosis.Translational cancer research · 2026Article
- Stromal cells contribute to progression, recurrence, and metastasis in oral squamous cell carcinoma: a call for therapy.Journal of translational medicine · 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
- Review
- Unraveling the impact of cancer-associated fibroblasts on lymphatic metastasis of head and neck squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Cancer-associated fibroblasts as facilitators in nasopharyngeal carcinoma progression via exosomal MMP13.Translational cancer research · 2025Article
- Review
- Halofuginone Disrupted Collagen Deposition via mTOR-eIF2α-ATF4 Axis to Enhance Chemosensitivity in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- New uses of halofuginone to treat cancer.Journal of pharmaceutical analysis · 2025Review
- Heterogeneity and therapeutic implications of cancer-associated fibroblasts in lung cancer: Recent advances and future perspectives.Chinese medical journal pulmonary and critical care medicine · 2024Review
- Targeted therapy for head and neck squamous cell carcinoma microenvironment.Frontiers in medicine · 2023Review
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Authors and funding
10 authors at 1 institution in 1 country.
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Abstract
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral and maxillofacial regions, with a high rate of metastasis. Cancer-associated fibroblasts (CAFs) play critical roles in tumor growth, metastasis and invasion, making them attractive therapeutic targets for cancer treatment. As an old anti-coccidiosis drug for poultry, Halofuginone (HF) has also been reported to possess anti-fibrosis and anti-cancer activities in the recent decades. However, whether it works by targeting CAFs in OSCC, and the mechanisms involved remain unclear. In the present study, we observed HF dose-dependently inhibits OSCC-derived CAF viability and proliferation. Meanwhile, HF decreased the expressions of α-SMA, FSP-1 and PDGFRβ, markers of the malignant phenotype of CAFs, both at mRNA and protein levels. Furthermore, functional studies demonstrated that HF dramatically attenuates the promotion effect of CAFs on OSCC cell migration and invasion. Mechanistically, the inhibition of MMP2 secretion and the upstream TGF-β/Smad2/3 signaling pathway played an important role in these processes. In the orthotopic transplanted tongue carcinoma in mice model, we confirmed that HF administration inhibited tumor growth and lymph node metastasis (LNM) with reduced CAF population, MMP2 expression and collagen deposition in tumor. Altogether, these results indicate that HF can inhibit the migration and invasion of OSCC by targeting CAFs, which will provide new ideas for the treatment of OSCC.
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