TY - JOUR
T1 - The effect of fascin 1 inhibition on head and neck squamous cell carcinoma cells
AU - Wahab, Awais
AU - Hyytiäinen, Aini
AU - Wahbi, Wafa
AU - Tuomainen, Katja
AU - Tervo, Sanni
AU - Conesa-Zamora, Pablo
AU - Jauhiainen, Laura
AU - Mäkinen, Laura K.
AU - Paavonen, Timo
AU - Toppila-Salmi, Sanna
AU - Salem, Abdelhakim
AU - Almangush, Alhadi
AU - Salo, Tuula
AU - Al-Samadi, Ahmed
N1 - Funding Information:
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. The funders took no part in the design or performance of the study. Funding consists of academic grants without any engagements considering the research project.
Publisher Copyright:
© 2021 European Journal of Oral Sciences
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - compound G2
KW - head and neck neoplasms
KW - irradiation
KW - neoplasm metastasis
KW - zebrafish
U2 - 10.1111/eos.12819
DO - 10.1111/eos.12819
M3 - Article
AN - SCOPUS:85111744343
VL - 129
JO - EUROPEAN JOURNAL OF ORAL SCIENCES
JF - EUROPEAN JOURNAL OF ORAL SCIENCES
SN - 0909-8836
IS - 6
M1 - e12819
ER -