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Wnt/β-catenin/Slug pathway contributes to tumor invasion and lymph node metastasis in head and neck squamous cell carcinoma

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Abstract

The canonical Wnt/β-catenin pathway is involved in diverse cancer development mechanisms, such as proliferation, migration, and invasion. However, its role in head and neck squamous cell carcinoma (HNSCC) remains largely unknown. We investigated whether the canonical Wnt/β-catenin signaling pathway acts as a controller of invasion and lymph node metastasis (LNM) in HNSCC. Loss of function experiments against the canonical Wnt/β-catenin pathway were conducted to evaluate its invasive and metastatic role in HNSCC cells. Slug was evaluated as a downstream protein in canonical Wnt/β-catenin-mediated invasion. In addition, canonical Wnt/β-catenin and Slug expression levels were examined in 119 HNSCC tissue samples to study the relevance of these proteins in LNM and prognosis of patients post-treatment. In vitro suppression of β-catenin expression led to decreased migration and invasion of HNSCC cells. Using an in vivo mouse orthotopic LNM model, a decrease in LNM was observed with mitigated β-catenin expression. Slug expression upregulation mediates invasion and LNM by the canonical Wnt/β-catenin pathway. Simultaneous expression of β-catenin and Slug is the major predictive factor of LNM and survival rate in patients with HNSCC. In conclusion, the canonical Wnt/β-catenin/Slug signaling axis significantly contributes to cancer cell invasion and LNM. Its blockade may be a treatment strategy for LNM and tumor recurrence in HNSCC.

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Funding

This work was supported by Konkuk University Hospital Grant (2019).

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Authors and Affiliations

  1. Department of Otorhinolaryngology – Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, #1, Hwayang-dong, Gwangin-gu, Seoul, 143-752, Korea

    Jung Hwa Moon & Young Chang Lim

  2. Department of Otorhinolaryngology – Head & Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

    Sang Hyuk Lee

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  1. Jung Hwa Moon
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Contributions

JHM, contributed to design, data acquisition, analysis, and interpretation, drafted the manuscript, critically revised the manuscript; SHL, contributed to data acquisition, analysis, and interpretation, drafted the manuscript; YCL, contributed to design, data analysis, and interpretation, drafted the manuscript, critically revised the manuscript. All authors gave final approval and agree to be accountable for all aspects of the work.

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Correspondence to Young Chang Lim.

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Moon, J.H., Lee, S.H. & Lim, Y.C. Wnt/β-catenin/Slug pathway contributes to tumor invasion and lymph node metastasis in head and neck squamous cell carcinoma. Clin Exp Metastasis 38, 163–174 (2021). https://doi.org/10.1007/s10585-021-10081-3

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  • DOI: https://doi.org/10.1007/s10585-021-10081-3

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