University of Oulu

Wahab, A., Hyytiäinen, A., Wahbi, W., Tuomainen, K., Tervo, S., Conesa‐Zamora, P., Jauhiainen, L., Mäkinen, L. K., Paavonen, T., Toppila‐Salmi, S., Salem, A., Almangush, A., Salo, T., & Al‐Samadi, A. (2021). The effect of fascin 1 inhibition on head and neck squamous cell carcinoma cells. European Journal of Oral Sciences, 129(6). https://doi.org/10.1111/eos.12819

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

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Author: Wahab, Awais1,2; Hyytiäinen, Aini1,2; Wahbi, Wafa1,2;
Organizations: 1Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland
2Translational Immunology Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
3Haartman Institute, University of Helsinki, Helsinki, Finland
4Department of Pathology, Faculty of Medicine and Health Technology and Fimlab Laboratories, Tampere University and Tampere University Hospital, Tampere, Finland
5Pathology and Histology Department, Health Faculty, Universidad Católica de Murcia, Campus de los Jerónimos, Guadalupe, Murcia, Spain
6Clinical Analysis Department, Group of Molecular Pathology and Pharmacogenetics, Biomedical Research Institute Murcia, Hospital Universitario Santa Lucía, Cartagena, Spain
7Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
8Skin and Allergy Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
9Department of Pathology, University of Helsinki, Helsinki, Finland
10Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
11Institute of Biomedicine, Pathology, University of Turku, Turku, Finland
12Cancer Research and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
13Medical Research Center Oulu, Oulu University HospitalUniversity of Oulu, Oulu, Finland
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2021122263013
Language: English
Published: John Wiley & Sons, 2021
Publish Date: 2022-08-04
Description:

Abstract

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.

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Series: European journal of oral sciences
ISSN: 0909-8836
ISSN-E: 1600-0722
ISSN-L: 0909-8836
Volume: 129
Issue: 6
Article number: e12819
DOI: 10.1111/eos.12819
OADOI: https://oadoi.org/10.1111/eos.12819
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: This research was funded by Sigrid Jusélius Foundation, the Cancer Society of Finland, Instituto de Salud Carlos III (Spanish Ministry of Health) and FEDER funds (ref: PI18/00144), the Oulu University Hospital MRC grant, the Helsinki University Central Hospital research funds, Research Fund of Finnish Otolaryngological Society, and Jane and Aatos Erkko Foundation.
Copyright information: © 2021 European Journal of Oral Sciences. This is the peer reviewed version of the following article: Wahab, A, Hyytiäinen, A, Wahbi, W, Tuomainen, K, Tervo, S, Conesa-Zamora, P, et al. The effect of fascin 1 inhibition on head and neck squamous cell carcinoma cells. Eur. J. Oral Sci. 2021; 1-11, which has been published in final form at https://doi.org/10.1111/eos.12819. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited."