Overexpression of FOXM1 is associated with metastases of nasopharyngeal carcinoma

Lizhu Jiang,Peng Wang,Hongyan Chen

doi:10.3109/03009734.2014.960053

Abstract

Background. The forkhead box M1 (FOXM1) transcription factor plays an important role in the metastases of many cancers. Down-regulation of FOXM1 by its inhibitor, thiostrepton, can inhibit the metastatic potential of some cancers; however, there are few studies regarding the functional signiﬁcance of FOXM1 and thiostrepton in the metastases of nasopharyngeal carcinoma (NPC) and the underlying mechanism.Methods. Expression of FOXM1 in NPC, normal nasopharyngeal tissues, a NPC cell line (C666-1), and a nasopharyngeal epithelial cell line (NP69) was investigated by immunohistochemical staining, qRT-PCR, and Western blot. The correlation between FOXM1 expression and the clinical characteristics of patients was analyzed. Moreover, the effects of thiostrepton on expression of FOXM1 in C666-1 and NP69 cells, and the invasion and migration ability of C666-1 cells were examined. The expressions of MMP-2, MMP-9, fascin-1, ezrin, and paxillin were determined after treatment with thiostrepton.Results. FOXM1 was overexpressed in NPC and C666-1 cells compared with normal nasopharyngeal tissues and NP69 cells. Overexpression of FOXM1 was associated with lymph node metastasis and advanced tumor stage. Moreover, thiostrepton inhibited expression of FOXM1 in C666-1 cells in a dose-dependent manner, but had a minimal effect on NP69 cells. Thiostrepton inhibited the migration and invasion ability of C666-1 cells by down-regulating the expression of MMP-2, MMP-9, fascin-1, and paxillin.Conclusions. Overexpression of FOXM1 is associated with metastases of NPC patients. Thiostrepton inhibits the metastatic ability of NPC cells by down-regulating the expression of FOXM1, MMP-2, MMP-9, fascin-1, and paxillin.

Highlights

Nasopharyngeal carcinoma (NPC), an Epstein–Barr virus-associated malignancy, is the most common head and neck cancer in China, with an incidence of 30–80/100,000 population/year in southern China [1]
65 nasopharyngeal carcinoma (NPC) specimens at different grades of malignancy and 20 non-cancerous nasopharyngeal tissue specimens were tested for forkhead box M1 (FOXM1) expression by immunohistochemistry
Recent studies have shown that FOXM1 and its inhibitor, thiostrepton, represented an attractive therapeutic target and novel anticancer drug in the fight against cancer [24,25,26,27]

Summary

Introduction

Nasopharyngeal carcinoma (NPC), an Epstein–Barr virus-associated malignancy, is the most common head and neck cancer in China, with an incidence of 30–80/100,000 population/year in southern China [1]. NPC has high invasive and metastatic features, and ~90% of patients show cervical lymph node metastasis at the time of initial diagnosis [2]. Radiotherapy with or without chemotherapy is the mainstream treatment approach for NPC patients; there are limitations in these therapeutic applications due to undesirable side effects, local recurrence, and metastasis [3]. Challenges in NPC treatment still exist, and novel therapeutic targets and new approaches for NPC treatment are urgently needed [4]. It has been shown that thiostrepton inhibits cell growth and induces apoptosis in a variety of human cancer cell lines by inhibiting FOXM1 expression [17,18,19]. In the current study we determined the expression of FOXM1 in NPC, normal nasopharyngeal tissues, a NPC cell line, and a nasopharyngeal epithelial cell line. The relationship between the expression of FOXM1 and clinicopathologic factors, such as TNM and clinical stage, was analyzed

Materials and methods

Results

Discussion