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

• Published in: European journal of oral sciences 2021-12, Vol.129 (6), p.e12819-n/a
• Main Authors: Wahab, Awais, Hyytiäinen, Aini, Wahbi, Wafa, Tuomainen, Katja, Tervo, Sanni, Conesa‐Zamora, Pablo, Jauhiainen, Laura, Mäkinen, Laura K., Paavonen, Timo, Toppila‐Salmi, Sanna, Salem, Abdelhakim, Almangush, Alhadi, Salo, Tuula, Al‐Samadi, Ahmed
• Format: Article
• Language: English
• Subjects: Cancer; Carrier Proteins - genetics; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement; compound G2; Cytotoxicity; Head & neck cancer; Head and neck carcinoma; head and neck neoplasms; Head and Neck Neoplasms - pathology; Humans; In vivo methods and tests; Invasiveness; Irradiation; Metastases; Metastasis; Microfilament Proteins - genetics; Neoplasm Invasiveness; neoplasm metastasis; Radiation; Reagents; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - pathology; Survival; Therapeutic targets; Tumors; zebrafish
• ISSN: 0909-8836; 1600-0722
• DOI: 10.1111/eos.12819

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.