Abstract
Background: The self-renewal and tumourigenicity of FoxM1 in nasopharyngeal carcinoma (NPC) remain largely unknown. In this study, we attempt to investigate the self-renewal and tumourigenicity of FoxM1 and its clinical significance in nasopharyngeal carcinoma (NPC).Methods: Several assays including cell counting Kit-8 (CCK-8) assays, colony formation, flow cytometry, immunofluorescence, tumor spheres, and mice model were used to detect the biological function of FoxM1 in NPC. The association between FoxM1 and clinical pathological features, and stem cell markers was analyzed using immunohistochemistry.Results: High expression of FoxM1 was prominently present in the T4 stages, cancer cells migrating into the stroma and vasculature. Overexpression of FoxM1 enhanced tumor proliferation, cell cycle progression, migration and stress fibers formation in vitro. In NPC tissues, FoxM1 correlated significantly with stem cells-related clinical pathological features including late clinical stage, tumor recurrence and distant metastasis. Meanwhile, FoxM1 linked closely with the expression levels of stem cell markers including Nanog, Sox2, and OCT4 in tumor samples, and also promoted the expression of these stemness-related genes in vitro. Moreover, FoxM1 conferred the self-renewal properties of cancer cells by increasing side populations (SP) cells and formed larger and more tumor spheres. Importantly, FoxM1 enhanced the ability of tumourigenicity of NPC cell lines in mice xenograft.Conclusions: We demonstrate that FoxM1 greatly induces cancer progression and cancer stem cell (CSC) features in NPC.
Highlights
Nasopharyngeal carcinoma (NPC) is a head and neck cancer that is endemic in Southern China and Southeast Asia [1]
High expression of FoxM1 was prominently present in the T4 stages, cancer cells migrating into the stroma and vasculature
We demonstrate that FoxM1 greatly induces cancer progression and cancer stem cell (CSC) features in nasopharyngeal carcinoma (NPC)
Summary
Nasopharyngeal carcinoma (NPC) is a head and neck cancer that is endemic in Southern China and Southeast Asia [1]. Cancer stem cells (CSCs) are defined by a subpopulation of cells within tumors have the capability of self-renewal and generating new tumors, are responsible for cancer unlimited proliferation, invasion, and late stage of patients [4, 5]. FoxM1 has an integral role in cancer initiation and cancer drug response [9, 10], indicating that FoxM1 might be a new and effective therapeutic target for the elimination of CSCs. For example, Hou et al reported that the depletion of FOXM1 sensitized the resistant cells to paclitaxel treatmente by regulating the gene transcription of abcc in NPC cell lines [10]. Up to now, the roles of FoxM1 in the tumorigenesis and stem cell-like features in NPC remain largely unknown. The self-renewal and tumourigenicity of FoxM1 in nasopharyngeal carcinoma (NPC) remain largely unknown. We attempt to investigate the self-renewal and tumourigenicity of FoxM1 and its clinical significance in nasopharyngeal carcinoma (NPC)
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