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

Fascin-1上调参与HIF-1α依赖的下咽鳞状细胞癌的侵袭和迁移

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作者:Mingqiang Bu, Xianfang Liu, Xiuxiu Liu, Wei Xu

Abstract

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)‑1α 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‑1α 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‑1α, 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.

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