The effect of fascin 1 inhibition on head and neck squamous cell carcinoma cells
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 (2021)
Mäkinen, Laura K.
Julkaisun pysyvä osoite on
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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