MNX1 reduces sensitivity to anoikis by activating TrkB in human glioma cells

Jiang,Lai; Chen,Shaojun; Zhao,Donggang; Yan,Jun; Chen,Jiemin; Yang,Chunlin; Zheng,Gang

doi:10.3892/mmr.2018.9329

MNX1 reduces sensitivity to anoikis by activating TrkB in human glioma cells

Authors:
- Lai Jiang
- Shaojun Chen
- Donggang Zhao
- Jun Yan
- Jiemin Chen
- Chunlin Yang
- Gang Zheng
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Affiliations: Department of Neurosurgery, The People's Hospital of China Three Gorges University, Yichang, Hubei 443000, P.R. China
Published online on: July 27, 2018 https://doi.org/10.3892/mmr.2018.9329
Pages: 3271-3279
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioma is the most common type of malignant intracranial tumor in adults and is associated with the highest mortality rate. Although surgery, radiotherapy, chemotherapy and other treatment methods have progressed, the median survival of patients with glioma is only 14‑15 months. Glioma cells are able to penetrate along blood vessels and invade into the surrounding normal brain tissue so that an overall resection of the tumor cannot be performed. In the process of metastasis, the resistance of cancer cells to anoikis has an important role. When tumor cells escape from their original environment, anoikis resistance aids their survival. In the present study, reverse transcription‑semi‑quantitative polymerase chain reaction (RT‑sqPCR), RT‑quantitative PCR and western blotting demonstrated that the transcription factor, motor neuron and pancreas homeobox 1 (MNX1), was ectopically expressed in glioma cells compared with normal HUVEC‑C human umbilical vein endothelial cells. Furthermore, its expression was higher in more malignant glioma cell lines (T98G and M059K) compared with the less malignant glioma cell line (U‑87 MG) and normal HUVEC‑C cells. An adhesion assay using fibronectin demonstrated that MNX1 and tyrosine kinase receptor B (TrkB) overexpression in HUVEC‑C and U‑87 MG cells reduced adhesion and forced them to suspend. Additionally, MNX1 and TrkB overexpression was demonstrated to increase the ability of cells to bypass anoikis. MNX1 and TrkB knockdown increased adhesion and promoted apoptosis after suspension. It was further demonstrated that MNX1 functioned as a transcription factor binding in the upstream regulatory region of TrkB to activate its expression. The results of the present study suggested that MNX1 may suppress the adhesion and apoptosis rates of tumor cells by activating TrkB. The results of the present study suggest that MNX1 may represent a novel therapeutic target for the treatment of gliomas.

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