Open AccessASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor
Author(s) -
Wang LiHong,
Yuan Ye,
Wang Jiao,
Luo Ying,
Lan Yang,
Ge Jia,
Li Lei,
Liu Feng,
Deng Qing,
Yan ZeXuan,
Liang Mei,
Wei Sen,
Liu XinDong,
Wang Yan,
Ping YiFang,
Shi Yu,
Yu ShiCang,
Zhang Xia,
Cui YouHong,
Yao XiaoHong,
Feng Hua,
Luo Tao,
Bian XiuWu
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202105938
Subject(s) - autophagy , phenotype , glioma , cancer research , biology , tumor progression , microbiology and biotechnology , cancer , genetics , gene , apoptosis
Abstract 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.