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The effect of fascin 1 inhibition on head and neck squamous cell carcinoma cells
Awais Wahab1,2, Aini Hyytiäinen1,2, Wafa Wahbi1,2
1Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.
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.
Insights
Targeting fascin 1 with compound G2 inhibits head and neck carcinoma (HNSCC) metastasis. High fascin 1 levels predict poorer survival in advanced HNSCC, suggesting its therapeutic and prognostic potential.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Therapeutics
Background:
- Fascin 1 promotes head and neck squamous cell carcinoma (HNSCC) metastasis.
- Targeting metastasis is crucial for improving HNSCC patient survival.
- Limited therapeutic options exist for HNSCC metastasis.
Purpose of the Study:
- To evaluate the anti-metastatic potential of fascin 1 inhibition using compound G2 in HNSCC.
- To assess the prognostic value of fascin 1 in HNSCC patients.
Main Methods:
- In vitro and in vivo studies of compound G2 effects on HNSCC cell migration, invasion, and metastasis.
- High-throughput screening (HTS) for compound G2 cytotoxicity, alone and with irradiation.
- Immunohistochemical analysis of fascin 1 expression and correlation with patient survival.
Main Results:
- Compound G2 significantly reduced HNSCC cell migration and invasion in vitro.
- Compound G2 inhibited HNSCC metastasis in vivo.
- High fascin 1 immunoexpression at the tumor invasive front correlated with increased cancer-specific mortality in advanced HNSCC.
- Compound G2 showed modest cytotoxicity, and irradiation did not enhance its activity synergistically.
Conclusions:
- Fascin 1 is a promising therapeutic target for anti-metastatic strategies in HNSCC.
- Fascin 1 immunoexpression serves as a valuable prognostic marker for HNSCC patients.
- Novel anti-metastatic agents targeting fascin 1 could enhance HNSCC treatment outcomes.
