FoxM1 overexpression promotes cell proliferation and migration and inhibits apoptosis in hypopharyngeal squamous cell carcinoma resulting in poor clinical prognosis

Chen,Yan; Liu,Yifei; Ni,Haosheng; Ding,Chuanjin; Zhang,Xiaobo; Zhang,Zhenxin

doi:10.3892/ijo.2017.4094

FoxM1 overexpression promotes cell proliferation and migration and inhibits apoptosis in hypopharyngeal squamous cell carcinoma resulting in poor clinical prognosis

Authors:
- Yan Chen
- Yifei Liu
- Haosheng Ni
- Chuanjin Ding
- Xiaobo Zhang
- Zhenxin Zhang
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Affiliations: Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: August 9, 2017 https://doi.org/10.3892/ijo.2017.4094
Pages: 1045-1054
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Forkhead box M1 (FoxM1), a member of the Fox family of transcriptional factors, is involved in the development of various human malignancies. However, the expression level of FoxM1 and its functional role in hypopharyngeal squamous cell carcinoma (HSCC) remained unclear to date. The aim of the present study was to investigate the FoxM1 expression in 63 HSCC and 20 adjacent normal tissues, as well as to evaluate its association with the clinicopathological parameters and its diagnostic value in HSCC. To further explore the biological function of FoxM1 in vitro, siRNAs were used to knockdown the expression of FoxM1 in the HSCC cell line Fadu. The results revealed that FoxM1 protein was highly expressed in HSCC tissues and that its high expression was closely associated with HSCC tumor differentiation (P=0.004), tumor size (P=0.002), clinical stage (P=0.001), lymph node metastasis (P=0.002), treatment (P=0.045) and expression of the proliferation marker Ki-67 (P<0.001). Additionally, the elevated expression of FoxM1 in HSCC patients consistently predicted a poor survival time. Knockdown of FoxM1 expression blocked Fadu cell proliferation and promoted apoptosis, and also led to the downregulation of cyclin A1 expression. Furthermore, decreased expression of FoxM1 markedly impeded cell migration and reversed the epithelial-mesenchymal transition phenotype, as indicated by decreased expression of vimentin and increased expression of E-cadherin in Fadu cells. These results indicate that FoxM1 may act as an oncogene and serve as a therapeutic target against malignant progression in HSCC.

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