Targeting Wnt/β-catenin-mediated upregulation of oncogenic NLGN3 suppresses cancer stem cells in glioblastoma

Glioblastoma (GBM) is the most malignant tumor in brain and is highly resistant to therapy. Clinical evidence suggests increased number of cancer stem cells (CSCs) may contribute to the failure of conventional therapies, but the mechanisms associated with acquisition of CSC properties in GBM are not...

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Bibliographic Details
Published in:Cell death & disease 2023-07, Vol.14 (7), p.423-423, Article 423
Main Authors: Yun, Eun-Jin, Kim, Donghwi, Kim, Sangwoo, Hsieh, Jer-Tsong, Baek, Seung Tae
Format: Article
Language:English
Subjects:
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Antibodies
beta Catenin - metabolism
Biochemistry
Biomedical and Life Sciences
Brain cancer
Brain tumors
Cell Biology
Cell Culture
Cell Line, Tumor
Cell Proliferation
Glioblastoma
Glioblastoma - drug therapy
Glioblastoma - genetics
Glioblastoma - metabolism
Humans
Immunology
Life Sciences
Neoplastic Stem Cells - metabolism
ras GTPase-Activating Proteins - metabolism
Signal transduction
Stem cells
Tumor Microenvironment
Up-Regulation
Wnt protein
Wnt Signaling Pathway
β-Catenin
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Summary:Glioblastoma (GBM) is the most malignant tumor in brain and is highly resistant to therapy. Clinical evidence suggests increased number of cancer stem cells (CSCs) may contribute to the failure of conventional therapies, but the mechanisms associated with acquisition of CSC properties in GBM are not fully understood. We found that DAB2IP suppresses CSC properties by targeting the synaptic proteins neuroligin 3 (NLGN3) in GBM. Furthermore, we showed that GBM-derived NLGN3 has an oncogenic function by inducing CSC properties within GBM. Moreover, elevated NLGN3 transcription mediated by Wnt/β-catenin signaling pathway resulted in increased secretion of NLGN3 into the surrounding tumor microenvironment. Both condition media containing NLGN3 and recombinant NLGN3 transformed neighboring cells to CSCs, suggesting NLGN3 as a critical component inducing CSC properties. Furthermore, targeting NLGN3-bearing CSCs using upstream Wnt/β-catenin inhibitors synergistically enhances the efficacy of conventional treatment. Hence, we unveiled the series of regulatory mechanisms for acquisition of CSC properties in GBM progression by Wnt/β-catenin-mediated NLGN3. These results may provide a new targeting strategy to improve the therapeutic efficacy of GBM treatments.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-023-05967-x