Upregulation of fascin-1 is involved in HIF-1α-dependent invasion and migration of hypopharyngeal squamous cell carcinoma

Fascin-1 is an actin-bundling protein, which specifically interacts with F-actin to form parallel actin bundles, and participates in the regulation of cell adhesion, interactions and migration. However, the expression and regulatory mechanisms of fascin-1 in hypopharyngeal squamous cell carcinoma (HSCC) remain poorly understood. The present study investigated the effects and underlying molecular mechanism of fascin-1 on the invasion and metastasis of HSCC. The results demonstrated that fascin-1 was overexpressed and correlated with lymph node metastasis and tumor-node-metastasis stage in HSCC tissues. Further in vitro study revealed that fascin-1 promoted cell morphology polarization to increase the motility of FaDu cells. In addition, fascin-1 significantly promoted the migration and invasion of FaDu cells. At the molecular level, fascin-1 promoted cell invasion and migration by upregulating matrix metalloproteinase-2 (MMP-2) expression in FaDu cells. Immunohistochemical analysis revealed that a correlation existed between hypoxia inducible factor (HIF)-1 alpha and fascin-1 expression in the HSCC tissues. Furthermore, the results from a cobalt chloride-induced hypoxia model demonstrated that fascin-1 may be upregulated by HIF-1 alpha in FaDu cells. Further analysis revealed that fascin-1 knockdown significantly decreased the invasion of cells under hypoxia and partially reversed hypoxia-induced MMP-2 expression under hypoxia in FaDu cells. In conclusion, fascin-1 was upregulated by HIF-1 alpha, and promoted the invasion and migration of HSCC cells; therefore, fascin-1 may provide a potential target for the treatment of invasion and metastasis in HSCC.