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ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor

Autophagy is a highly conserved process that is vital for tumor progression and treatment response. Although autophagy is proposed to maintain the stemness phenotype in adult diffuse glioma, the molecular basis of the link between autophagy and stemness is poorly understood, which makes it impossibl...

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Autores principales: Wang, Li‐Hong, Yuan, Ye, Wang, Jiao, Luo, Ying, Lan, Yang, Ge, Jia, Li, Lei, Liu, Feng, Deng, Qing, Yan, Ze‐Xuan, Liang, Mei, Wei, Sen, Liu, Xin‐Dong, Wang, Yan, Ping, Yi‐Fang, Shi, Yu, Yu, Shi‐Cang, Zhang, Xia, Cui, You‐Hong, Yao, Xiao‐Hong, Feng, Hua, Luo, Tao, Bian, Xiu‐Wu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9507388/
https://www.ncbi.nlm.nih.gov/pubmed/35882624
http://dx.doi.org/10.1002/advs.202105938
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author Wang, Li‐Hong
Yuan, Ye
Wang, Jiao
Luo, Ying
Lan, Yang
Ge, Jia
Li, Lei
Liu, Feng
Deng, Qing
Yan, Ze‐Xuan
Liang, Mei
Wei, Sen
Liu, Xin‐Dong
Wang, Yan
Ping, Yi‐Fang
Shi, Yu
Yu, Shi‐Cang
Zhang, Xia
Cui, You‐Hong
Yao, Xiao‐Hong
Feng, Hua
Luo, Tao
Bian, Xiu‐Wu
author_facet Wang, Li‐Hong
Yuan, Ye
Wang, Jiao
Luo, Ying
Lan, Yang
Ge, Jia
Li, Lei
Liu, Feng
Deng, Qing
Yan, Ze‐Xuan
Liang, Mei
Wei, Sen
Liu, Xin‐Dong
Wang, Yan
Ping, Yi‐Fang
Shi, Yu
Yu, Shi‐Cang
Zhang, Xia
Cui, You‐Hong
Yao, Xiao‐Hong
Feng, Hua
Luo, Tao
Bian, Xiu‐Wu
author_sort Wang, Li‐Hong
collection PubMed
description Autophagy is a highly conserved process that is vital for tumor progression and treatment response. Although autophagy is proposed to maintain the stemness phenotype in adult diffuse glioma, the molecular basis of the link between autophagy and stemness is poorly understood, which makes it impossible to effectively screen for the population that will benefit from autophagy‐targeted treatment. Here, ATG9B as essential for self‐renewal capacity and tumor‐propagation potential is identified. Notably, ASCL2 transcriptionally regulates the expression of ATG9B to maintain stemness properties. The ASCL2‐ATG9B axis is an independent prognostic biomarker and indicator of autophagic activity. Furthermore, the highly effective blood–brain barrier (BBB)‐permeable autophagy inhibitor ROC‐325, which can significantly inhibit the progression of ASCL2‐ATG9B axis(High) gliomas as a single agent is investigated. These data demonstrate that a new ASCL2‐ATG9B signaling axis is crucial for maintaining the stemness phenotype and tumor progression, revealing a potential autophagy inhibition strategy for adult diffuse gliomas.
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spelling pubmed-95073882022-09-30 ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor Wang, Li‐Hong Yuan, Ye Wang, Jiao Luo, Ying Lan, Yang Ge, Jia Li, Lei Liu, Feng Deng, Qing Yan, Ze‐Xuan Liang, Mei Wei, Sen Liu, Xin‐Dong Wang, Yan Ping, Yi‐Fang Shi, Yu Yu, Shi‐Cang Zhang, Xia Cui, You‐Hong Yao, Xiao‐Hong Feng, Hua Luo, Tao Bian, Xiu‐Wu Adv Sci (Weinh) Research Articles Autophagy is a highly conserved process that is vital for tumor progression and treatment response. Although autophagy is proposed to maintain the stemness phenotype in adult diffuse glioma, the molecular basis of the link between autophagy and stemness is poorly understood, which makes it impossible to effectively screen for the population that will benefit from autophagy‐targeted treatment. Here, ATG9B as essential for self‐renewal capacity and tumor‐propagation potential is identified. Notably, ASCL2 transcriptionally regulates the expression of ATG9B to maintain stemness properties. The ASCL2‐ATG9B axis is an independent prognostic biomarker and indicator of autophagic activity. Furthermore, the highly effective blood–brain barrier (BBB)‐permeable autophagy inhibitor ROC‐325, which can significantly inhibit the progression of ASCL2‐ATG9B axis(High) gliomas as a single agent is investigated. These data demonstrate that a new ASCL2‐ATG9B signaling axis is crucial for maintaining the stemness phenotype and tumor progression, revealing a potential autophagy inhibition strategy for adult diffuse gliomas. John Wiley and Sons Inc. 2022-07-26 /pmc/articles/PMC9507388/ /pubmed/35882624 http://dx.doi.org/10.1002/advs.202105938 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Wang, Li‐Hong
Yuan, Ye
Wang, Jiao
Luo, Ying
Lan, Yang
Ge, Jia
Li, Lei
Liu, Feng
Deng, Qing
Yan, Ze‐Xuan
Liang, Mei
Wei, Sen
Liu, Xin‐Dong
Wang, Yan
Ping, Yi‐Fang
Shi, Yu
Yu, Shi‐Cang
Zhang, Xia
Cui, You‐Hong
Yao, Xiao‐Hong
Feng, Hua
Luo, Tao
Bian, Xiu‐Wu
ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor
title ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor
title_full ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor
title_fullStr ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor
title_full_unstemmed ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor
title_short ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor
title_sort ascl2 maintains stemness phenotype through atg9b and sensitizes gliomas to autophagy inhibitor
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9507388/
https://www.ncbi.nlm.nih.gov/pubmed/35882624
http://dx.doi.org/10.1002/advs.202105938
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