ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor. Issue 27 (26th July 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Advanced science. Volume 9:Issue 27(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-07-26
• Subjects: autophagy -- adult diffuse gliomas -- ATG9B -- ASCL2 -- stemness -- ROC‐325; Science -- Periodicals; 505
• DOI: 10.1002/advs.202105938
• Languages: English
• ISSNs: 2198-3844

Abstract

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. Abstract : A novel ASCL2‐ATG9B axis for self‐renewing capacity and tumor‐propagating potential in adult diffuse gliomas is identified. Furthermore, high blood–brain barrier permeable and effective autophagic inhibitor ROC‐325, which can significantly inhibit the progression of ASCL2‐ATG9B axis High gliomas as a single agent is screened. This study indicates a potential autophagy inhibition strategy for ASCL2‐ATG9B axis High glioma patients.