The effect of fascin 1 inhibition on head and neck squamous cell carcinoma cells.

Autor: Wahab A; Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.; Translational Immunology Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Hyytiäinen A; Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.; Translational Immunology Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Wahbi W; Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.; Translational Immunology Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Tuomainen K; Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.; Translational Immunology Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Tervo S; Haartman Institute, University of Helsinki, Helsinki, Finland.; Department of Pathology, Faculty of Medicine and Health Technology and Fimlab Laboratories, Tampere University and Tampere University Hospital, Tampere, Finland., Conesa-Zamora P; Pathology and Histology Department, Health Faculty, Universidad Católica de Murcia, Campus de los Jerónimos, Guadalupe, Murcia, Spain.; Clinical Analysis Department, Group of Molecular Pathology and Pharmacogenetics, Biomedical Research Institute Murcia, Hospital Universitario Santa Lucía, Cartagena, Spain., Jauhiainen L; Haartman Institute, University of Helsinki, Helsinki, Finland., Mäkinen LK; Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Paavonen T; Department of Pathology, Faculty of Medicine and Health Technology and Fimlab Laboratories, Tampere University and Tampere University Hospital, Tampere, Finland., Toppila-Salmi S; Skin and Allergy Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Salem A; Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.; Translational Immunology Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Almangush A; Department of Pathology, University of Helsinki, Helsinki, Finland.; Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Institute of Biomedicine, Pathology, University of Turku, Turku, Finland., Salo T; Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.; Translational Immunology Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Cancer Research and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.; Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland., Al-Samadi A; Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.; Translational Immunology Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Jazyk: angličtina
Zdroj: European journal of oral sciences [Eur J Oral Sci] 2021 Dec; Vol. 129 (6), pp. e12819. Date of Electronic Publication: 2021 Aug 04.
DOI: 10.1111/eos.12819
Abstrakt: Fascin 1 plays important pro-metastatic roles in head and neck carcinoma (HNSCC) migration, invasion, and metastasis. However, limited advancement in targeting metastasis remains a major obstacle in improving HNSCC patients' survival. Therefore, we assessed the therapeutic potential of fascin 1 targeted inhibition and its potential prognostic value in HNSCC patients. Using in vitro and in vivo approaches, we investigated the effect of compound G2, a novel fascin 1 inhibitor, on HNSCC cells migration, invasion, and metastasis. High-throughput screening (HTS) was used to assess cytotoxic activity of compound G2 alone or combined with irradiation. We also evaluated the prognostic potential of fascin 1 in HNSCC patients. Interestingly, compound G2 reduced carcinoma cells migration and invasion in vitro and inhibited metastasis in vivo. Moreover, HTS revealed a modest cytotoxic activity of the compound G2 on HNSCC cell lines. Irradiation did not synergistically enhance the compound G2-mediated cytotoxic activity. Survival analyses showed that high fascin 1 immunoexpression, at the tumor invasive front, was associated with cancer-specific mortality in the advanced stages of HNSCC. Collectively, our findings suggest that fascin 1 represents a promising anti-metastatic therapeutic target and a useful prognostic marker in patients with HNSCC. Novel anti-metastatic agents could provide a valuable addition to cancer therapy.
(© 2021 The Authors. European Journal of Oral Sciences published by John Wiley & Sons Ltd on behalf of Scandinavian Division of the International Association for Dental Research.)
Databáze: MEDLINE
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