Cargando…
n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma
Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20–21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem c...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343907/ https://www.ncbi.nlm.nih.gov/pubmed/28208648 http://dx.doi.org/10.3390/ijms18020372 |
_version_ | 1782513451405410304 |
---|---|
author | Yen, Ssu-Yin Chuang, Hong-Meng Huang, Mao-Hsuan Lin, Shinn-Zong Chiou, Tzyy-Wen Harn, Horng-Jyh |
author_facet | Yen, Ssu-Yin Chuang, Hong-Meng Huang, Mao-Hsuan Lin, Shinn-Zong Chiou, Tzyy-Wen Harn, Horng-Jyh |
author_sort | Yen, Ssu-Yin |
collection | PubMed |
description | Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20–21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival. In this study, we used a small molecule, n-butylidenephthalide (BP), to assess the anti-GBM stem-like cells potential, and then tried to find out the associated genes involved with regulation in migration and invasion. We demonstrated that BP reduced the expression of AXL and stemness related genes in a dose-dependent manner. The migratory and invasive capabilities of GBM stem-like cells could be reduced by AXL/EZH2. Finally, in the overexpression of AXL, EZH2 and Sox2 by transfection in GBM stem-like cells, we found that AXL/EZH2/TGF-β1, but not Sox2, might be a key regulator in tumor invasion, migration and EMT. These results might help in the development of a new anticancer compound and can be a target for treating GBM. |
format | Online Article Text |
id | pubmed-5343907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-53439072017-03-16 n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma Yen, Ssu-Yin Chuang, Hong-Meng Huang, Mao-Hsuan Lin, Shinn-Zong Chiou, Tzyy-Wen Harn, Horng-Jyh Int J Mol Sci Article Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20–21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival. In this study, we used a small molecule, n-butylidenephthalide (BP), to assess the anti-GBM stem-like cells potential, and then tried to find out the associated genes involved with regulation in migration and invasion. We demonstrated that BP reduced the expression of AXL and stemness related genes in a dose-dependent manner. The migratory and invasive capabilities of GBM stem-like cells could be reduced by AXL/EZH2. Finally, in the overexpression of AXL, EZH2 and Sox2 by transfection in GBM stem-like cells, we found that AXL/EZH2/TGF-β1, but not Sox2, might be a key regulator in tumor invasion, migration and EMT. These results might help in the development of a new anticancer compound and can be a target for treating GBM. MDPI 2017-02-10 /pmc/articles/PMC5343907/ /pubmed/28208648 http://dx.doi.org/10.3390/ijms18020372 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yen, Ssu-Yin Chuang, Hong-Meng Huang, Mao-Hsuan Lin, Shinn-Zong Chiou, Tzyy-Wen Harn, Horng-Jyh n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma |
title | n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma |
title_full | n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma |
title_fullStr | n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma |
title_full_unstemmed | n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma |
title_short | n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma |
title_sort | n-butylidenephthalide regulated tumor stem cell genes ezh2/axl and reduced its migration and invasion in glioblastoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343907/ https://www.ncbi.nlm.nih.gov/pubmed/28208648 http://dx.doi.org/10.3390/ijms18020372 |
work_keys_str_mv | AT yenssuyin nbutylidenephthalideregulatedtumorstemcellgenesezh2axlandreduceditsmigrationandinvasioninglioblastoma AT chuanghongmeng nbutylidenephthalideregulatedtumorstemcellgenesezh2axlandreduceditsmigrationandinvasioninglioblastoma AT huangmaohsuan nbutylidenephthalideregulatedtumorstemcellgenesezh2axlandreduceditsmigrationandinvasioninglioblastoma AT linshinnzong nbutylidenephthalideregulatedtumorstemcellgenesezh2axlandreduceditsmigrationandinvasioninglioblastoma AT chioutzyywen nbutylidenephthalideregulatedtumorstemcellgenesezh2axlandreduceditsmigrationandinvasioninglioblastoma AT harnhorngjyh nbutylidenephthalideregulatedtumorstemcellgenesezh2axlandreduceditsmigrationandinvasioninglioblastoma |