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

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Autophagy is vital for tumor progression and treatment response.
• The molecular link between autophagy and stemness in adult diffuse glioma remains poorly understood.
• Effective screening for patients benefiting from autophagy-targeted treatment is hindered by this knowledge gap.

Purpose of the Study:

• To elucidate the molecular basis of the link between autophagy and stemness in adult diffuse glioma.
• To identify novel biomarkers for predicting treatment response.
• To investigate a potential therapeutic strategy targeting autophagy in gliomas.

Main Methods:

• Identification of ATG9B as essential for self-renewal and tumor propagation.
• Demonstration of ASCL2's transcriptional regulation of ATG9B expression.
• Evaluation of the ASCL2-ATG9B axis as a prognostic biomarker.
• Investigation of the blood-brain barrier-permeable autophagy inhibitor ROC-325 in ASCL2-ATG9B axis^High gliomas.

Main Results:

• ATG9B was identified as critical for glioma self-renewal and tumor propagation.
• The ASCL2-ATG9B signaling axis was established as a key regulator of stemness properties.
• The ASCL2-ATG9B axis serves as an independent prognostic biomarker and indicator of autophagic activity.
• The autophagy inhibitor ROC-325 demonstrated significant inhibition of ASCL2-ATG9B axis^High glioma progression.

Conclusions:

• A novel ASCL2-ATG9B signaling axis is crucial for maintaining the stemness phenotype and tumor progression in adult diffuse gliomas.
• This axis represents a potential therapeutic target for autophagy inhibition strategies.
• The findings pave the way for improved patient stratification and targeted treatment approaches for gliomas.