Upregulation of fascin-1 is involved in HIF-1α-dependent invasion and migration of hypopharyngeal squamous cell carcinoma
Upregulation of fascin-1 is involved in HIF-1α-dependent invasion and migration of hypopharyngeal squamous cell carcinoma
复制标题
Fascin-1的上调参与HIF-1α依赖性下咽鳞状细胞癌的侵袭和迁移
DOI：
10.3892/ijo.2019.4827
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发表时间：
2019-08-01
影响因子：
5.2
通讯作者：
Xu, Wei
中科院分区：
文献类型：
--
作者：
Bu, Mingqiang;Liu, Xianfang;Xu, Wei
Fascin-1是一种肌动蛋白成束蛋白，与F-肌动蛋白特异性相互作用形成平行肌动蛋白束，参与细胞粘附、相互作用和迁移的调节。然而，Fascin-1在下咽鳞状细胞癌（HSCC）中的表达及其调控机制仍知之甚少。本研究旨在探讨fascin-1在HSCC侵袭转移中的作用及其分子机制。Fascin-1在HSCC组织中呈高表达，并与淋巴结转移和肿瘤淋巴结转移分期相关。进一步的体外研究表明，fascin-1促进细胞形态极化，以增加FaDu细胞的运动性。此外，fascin-1显著促进FaDu细胞的迁移和侵袭。在分子水平上，fascin-1通过上调FaDu细胞中基质金属蛋白酶-2（MMP-2）的表达来促进细胞的侵袭和迁移。免疫组化分析显示HSCC组织中缺氧诱导因子（HIF）-1 α和fascin-1的表达存在相关性。此外，氯化钴诱导的缺氧模型的结果表明，fascin-1可能被FaDu细胞中的HIF-1 α上调。进一步的分析显示，fascin-1敲低显著降低了FaDu细胞在缺氧下的侵袭力，并部分逆转了缺氧诱导的FaDu细胞在缺氧下的MMP-2表达。结论：Fascin-1在HIF-1 α诱导下表达上调，促进了HSCC细胞的侵袭和迁移，可能成为HSCC侵袭和转移治疗的潜在靶点。
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.