Musashi-1 promotes chemoresistant granule formation by PKR/eIF2α signalling cascade in refractory glioblastoma

Hsiao Yun Chen, Liang Ting Lin, Mong Lien Wang, Kun-Ling Tsai, Pin I. Huang, Yi Ping Yang, Yi Yen Lee, Yi Wei Chen, Wen Liang Lo, Yuan Tzu Lan, Shih Hwa Chiou, Chien Min Lin, Hsin I. Ma, Ming Teh Chen

研究成果: Article

5 引文 (Scopus)

摘要

Musashi-1 (MSI1), one of the RNA-binding proteins, is abundantly found not only in neural stem cells but also in several cancer tissues and has been reported to act as a positive regulator of cancer progression. Growing evidence indicates that PKR and eIF2α play pivotal roles in the stimulation of stress granule formation as well as in the subsequent translation modulation in response to stressful conditions; however, little is known about whether MSI1 is involved in this PKR/eIF2α cancer stem cell-enhancing machinery. In this study, we demonstrated that MSI1 promotes human glioblastoma multiforme (GBM) stem cells and enhances chemoresistance when exposed to sublethal stress. The overexpression of MSI1 leads to a protective effect in mitigating drug-induced cell death, thus facilitating the formation of chemoresistant stress granules (SGs) in response to arsenic trioxide (ATO) treatment. SG components, such as PKR and eIF2α, were dominantly activated and assembled, while ATO was engaged. The activated PKR and eIF2α contribute to the downstream enhancement of stem cell genes, thereby promoting the progression of GBM. The silencing of MSI1 or PKR both obviously withdrew the phenomena. Taken together, our findings indicate that MSI1 plays a leading role in stress granule formation that grants cancer stem cell properties and chemoresistant stress granules in GBM, in response to stressful conditions via the PKR/eIF2α signalling cascade.

原文English
頁(從 - 到)1850-1861
頁數12
期刊Biochimica et Biophysica Acta - Molecular Basis of Disease
1864
發行號5
DOIs
出版狀態Published - 2018 五月 1

指紋

Glioblastoma
Neoplastic Stem Cells
Stem Cells
RNA-Binding Proteins
Neural Stem Cells
Organized Financing
Neoplasms
Cell Death
Pharmaceutical Preparations
Genes
arsenic trioxide

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology

引用此文

Chen, Hsiao Yun ; Lin, Liang Ting ; Wang, Mong Lien ; Tsai, Kun-Ling ; Huang, Pin I. ; Yang, Yi Ping ; Lee, Yi Yen ; Chen, Yi Wei ; Lo, Wen Liang ; Lan, Yuan Tzu ; Chiou, Shih Hwa ; Lin, Chien Min ; Ma, Hsin I. ; Chen, Ming Teh. / Musashi-1 promotes chemoresistant granule formation by PKR/eIF2α signalling cascade in refractory glioblastoma. 於: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2018 ; 卷 1864, 編號 5. 頁 1850-1861.
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title = "Musashi-1 promotes chemoresistant granule formation by PKR/eIF2α signalling cascade in refractory glioblastoma",
abstract = "Musashi-1 (MSI1), one of the RNA-binding proteins, is abundantly found not only in neural stem cells but also in several cancer tissues and has been reported to act as a positive regulator of cancer progression. Growing evidence indicates that PKR and eIF2α play pivotal roles in the stimulation of stress granule formation as well as in the subsequent translation modulation in response to stressful conditions; however, little is known about whether MSI1 is involved in this PKR/eIF2α cancer stem cell-enhancing machinery. In this study, we demonstrated that MSI1 promotes human glioblastoma multiforme (GBM) stem cells and enhances chemoresistance when exposed to sublethal stress. The overexpression of MSI1 leads to a protective effect in mitigating drug-induced cell death, thus facilitating the formation of chemoresistant stress granules (SGs) in response to arsenic trioxide (ATO) treatment. SG components, such as PKR and eIF2α, were dominantly activated and assembled, while ATO was engaged. The activated PKR and eIF2α contribute to the downstream enhancement of stem cell genes, thereby promoting the progression of GBM. The silencing of MSI1 or PKR both obviously withdrew the phenomena. Taken together, our findings indicate that MSI1 plays a leading role in stress granule formation that grants cancer stem cell properties and chemoresistant stress granules in GBM, in response to stressful conditions via the PKR/eIF2α signalling cascade.",
author = "Chen, {Hsiao Yun} and Lin, {Liang Ting} and Wang, {Mong Lien} and Kun-Ling Tsai and Huang, {Pin I.} and Yang, {Yi Ping} and Lee, {Yi Yen} and Chen, {Yi Wei} and Lo, {Wen Liang} and Lan, {Yuan Tzu} and Chiou, {Shih Hwa} and Lin, {Chien Min} and Ma, {Hsin I.} and Chen, {Ming Teh}",
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Chen, HY, Lin, LT, Wang, ML, Tsai, K-L, Huang, PI, Yang, YP, Lee, YY, Chen, YW, Lo, WL, Lan, YT, Chiou, SH, Lin, CM, Ma, HI & Chen, MT 2018, 'Musashi-1 promotes chemoresistant granule formation by PKR/eIF2α signalling cascade in refractory glioblastoma', Biochimica et Biophysica Acta - Molecular Basis of Disease, 卷 1864, 編號 5, 頁 1850-1861. https://doi.org/10.1016/j.bbadis.2018.02.017

Musashi-1 promotes chemoresistant granule formation by PKR/eIF2α signalling cascade in refractory glioblastoma. / Chen, Hsiao Yun; Lin, Liang Ting; Wang, Mong Lien; Tsai, Kun-Ling; Huang, Pin I.; Yang, Yi Ping; Lee, Yi Yen; Chen, Yi Wei; Lo, Wen Liang; Lan, Yuan Tzu; Chiou, Shih Hwa; Lin, Chien Min; Ma, Hsin I.; Chen, Ming Teh.

於: Biochimica et Biophysica Acta - Molecular Basis of Disease, 卷 1864, 編號 5, 01.05.2018, p. 1850-1861.

研究成果: Article

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T1 - Musashi-1 promotes chemoresistant granule formation by PKR/eIF2α signalling cascade in refractory glioblastoma

AU - Chen, Hsiao Yun

AU - Lin, Liang Ting

AU - Wang, Mong Lien

AU - Tsai, Kun-Ling

AU - Huang, Pin I.

AU - Yang, Yi Ping

AU - Lee, Yi Yen

AU - Chen, Yi Wei

AU - Lo, Wen Liang

AU - Lan, Yuan Tzu

AU - Chiou, Shih Hwa

AU - Lin, Chien Min

AU - Ma, Hsin I.

AU - Chen, Ming Teh

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Musashi-1 (MSI1), one of the RNA-binding proteins, is abundantly found not only in neural stem cells but also in several cancer tissues and has been reported to act as a positive regulator of cancer progression. Growing evidence indicates that PKR and eIF2α play pivotal roles in the stimulation of stress granule formation as well as in the subsequent translation modulation in response to stressful conditions; however, little is known about whether MSI1 is involved in this PKR/eIF2α cancer stem cell-enhancing machinery. In this study, we demonstrated that MSI1 promotes human glioblastoma multiforme (GBM) stem cells and enhances chemoresistance when exposed to sublethal stress. The overexpression of MSI1 leads to a protective effect in mitigating drug-induced cell death, thus facilitating the formation of chemoresistant stress granules (SGs) in response to arsenic trioxide (ATO) treatment. SG components, such as PKR and eIF2α, were dominantly activated and assembled, while ATO was engaged. The activated PKR and eIF2α contribute to the downstream enhancement of stem cell genes, thereby promoting the progression of GBM. The silencing of MSI1 or PKR both obviously withdrew the phenomena. Taken together, our findings indicate that MSI1 plays a leading role in stress granule formation that grants cancer stem cell properties and chemoresistant stress granules in GBM, in response to stressful conditions via the PKR/eIF2α signalling cascade.

AB - Musashi-1 (MSI1), one of the RNA-binding proteins, is abundantly found not only in neural stem cells but also in several cancer tissues and has been reported to act as a positive regulator of cancer progression. Growing evidence indicates that PKR and eIF2α play pivotal roles in the stimulation of stress granule formation as well as in the subsequent translation modulation in response to stressful conditions; however, little is known about whether MSI1 is involved in this PKR/eIF2α cancer stem cell-enhancing machinery. In this study, we demonstrated that MSI1 promotes human glioblastoma multiforme (GBM) stem cells and enhances chemoresistance when exposed to sublethal stress. The overexpression of MSI1 leads to a protective effect in mitigating drug-induced cell death, thus facilitating the formation of chemoresistant stress granules (SGs) in response to arsenic trioxide (ATO) treatment. SG components, such as PKR and eIF2α, were dominantly activated and assembled, while ATO was engaged. The activated PKR and eIF2α contribute to the downstream enhancement of stem cell genes, thereby promoting the progression of GBM. The silencing of MSI1 or PKR both obviously withdrew the phenomena. Taken together, our findings indicate that MSI1 plays a leading role in stress granule formation that grants cancer stem cell properties and chemoresistant stress granules in GBM, in response to stressful conditions via the PKR/eIF2α signalling cascade.

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