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

Awais Wahab, Aini Hyytiäinen, Wafa Wahbi, Katja Tuomainen, Sanni Tervo, Pablo Conesa-Zamora, Laura Jauhiainen, Laura K. Mäkinen, Timo Paavonen, Sanna Toppila-Salmi, Abdelhakim Salem, Alhadi Almangush, Tuula Salo, Ahmed Al-Samadi

Research output: Contribution to journalArticleScientificpeer-review

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.

Original languageEnglish
JournalEUROPEAN JOURNAL OF ORAL SCIENCES
DOIs
Publication statusE-pub ahead of print - 4 Aug 2021
Publication typeA1 Journal article-refereed

Keywords

  • compound G2
  • head and neck neoplasms
  • irradiation
  • neoplasm metastasis
  • zebrafish

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Dentistry(all)

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