FOXK1 promotes glioblastoma proliferation and metastasis through activation of Snail transcription

Xu,Haitao; Huang,Shulan; Zhu,Xiaonan; Zhang,Wangcheng; Zhang,Xiangyang

doi:10.3892/etm.2018.5732

FOXK1 promotes glioblastoma proliferation and metastasis through activation of Snail transcription

Authors:
- Haitao Xu
- Shulan Huang
- Xiaonan Zhu
- Wangcheng Zhang
- Xiangyang Zhang
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Affiliations: Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: January 10, 2018 https://doi.org/10.3892/etm.2018.5732
Pages: 3108-3116

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Abstract

Forkhead box K1 (FOXK1) has been identified to have a crucial function in development and oncogenesis. However, its role in glioblastoma has remained largely elusive and was therefore assessed in the present study. In human glioblastoma multiforme (GBM) tissue samples, FOXK1 was determined to be highly expressed compared with adjacent normal tissue samples. In addition, high levels of FOXK1 were detected in the T98G and LN18 GBM cell lines as compare with those in normal human astrocytes. Of note, high expression of FOXK1 was revealed to be associated with metastasis and tumor size. Loss‑ and gain‑of‑function experiments were then performed to determine whether FOXK1 regulates epithelial to mesenchymal transition (EMT) and cell proliferation. Knockdown of FOXK1 significantly suppressed EMT and metastasis of GBM cells, while ectopic expression of FOXK1 promoted them. A luciferase reporter assay and a chromatin immunoprecipitation assay revealed that FOXK1 activated the transcription of Snail. In addition, as the results indicated that FOXK1 promotes GBM cell proliferation, the potential effect of FOXK1 on the cell cycle and apoptosis were further assessed. While FOXK1 had no effect on apoptosis, it promoted cell proliferation via enhancing the S‑phase population. In brief, the present study indicated that FOXK1 acts as an oncogene with a key function in glioblastoma cell proliferation and EMT.

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