4.8 Article

The Interaction between Collagen 1 and High Mannose Type CD133 Up-Regulates Glutamine Transporter SLC1A5 to Promote the Tumorigenesis of Glioblastoma Stem Cells

Journal

ADVANCED SCIENCE
Volume -, Issue -, Pages -

Publisher

WILEY
DOI: 10.1002/advs.202306715

Keywords

CD133; COL1; glioma stem cell; tumorigenesis

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The study identifies COL1 as an extracellular binding molecule of cancer stem cells marker CD133. The interaction between COL1 and CD133 enhances the tumorigenesis of GSCs by up-regulating SLC1A5-dependent glutamine uptake. This finding provides a new mechanism underlying the cross-talk between GSCs and ECM microenvironment.
Targeting the niche components surrounding glioblastoma stem cells (GSCs) helps to develop more effective glioblastoma treatments. However, the mechanisms underlying the crosstalk between GSCs and microenvironment remain largely unknown. Clarifying the extracellular molecules binding to GSCs marker CD133 helps to elucidate the mechanism of the communication between GSCs and the microenvironment. Here, it is found that the extracellular domain of high mannose type CD133 physically interacts with Collagen 1 (COL1) in GSCs. COL1, mainly secreted by cancer-associated fibroblasts, is a niche component for GSCs. COL1 enhances the interaction between CD133 and p85 and activates Akt phosphorylation. Activation of Akt pathway increases transcription factor ATF4 protein level, subsequently enhances SLC1A5-dependent glutamine uptake and glutathione synthesis. The inhibition of CD133-COL1 interaction or down-regulation of SLC1A5 reduces COL1-accelerated GSCs self-renewal and tumorigenesis. Analysis of glioma samples reveals that the level of COL1 is correlated with histopathological grade of glioma and the expression of SLC1A5. Collectively, COL1, a niche component for GSCs, enhances the tumorigenesis of GSCs partially through CD133-Akt-SLC1A5 signaling axis, providing a new mechanism underlying the cross-talk between GSCs and extracellular matrix (ECM) microenvironment. This study identifies COL1 as an extracellular binding molecule of cancer stem cells marker CD133. The interaction between COL1 and CD133 enhances the interaction between CD133 and p85, up-regulates SLC1A5-dependent glutamine uptake, and promotes the tumorigenesis of GSCs. This finding provides a new mechanism underlying the cross-talk between GSCs and ECM microenvironment.image

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