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

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Hsiao-Yun ChenMing-Teh Chen

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 MS...Continue Reading

Citations

May 6, 2019·International Journal of Molecular Sciences·Fernanda Cristina Sulla LupinacciGlaucia Noeli Maroso Hajj
May 7, 2019·International Journal of Molecular Medicine·Chen-Fei WangYu-Nong Wu
Jul 11, 2019·Oncology Letters·Jorge Organista-NavaBerenice Illades-Aguiar
Dec 16, 2020·Cellular Signalling·Glaucia Noeli Maroso HajjMartin Roffe
Dec 16, 2020·Cancer Cell International·Aliaksandr A YarmishynMong-Lien Wang
Jun 3, 2021·Biology·Nadine BleyStefan Hüttelmaier
May 25, 2021·Journal of the Chinese Medical Association : JCMA·Xian LiuLiang-Ting Lin
Oct 5, 2021·Frontiers in Cell and Developmental Biology·Mohammad Reza AsadiMaryam Rezazadeh

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