Genetic Manipulation of Adhesion GPCR CD97/ADGRE5 Modulates Invasion in Patient-Derived Glioma Stem Cells

Researchers examined CD97 function in primary patient-derived glioma stem cells obtained from five glioblastoma tumors, belonging to three major genetic subtypes.
[Journal of Neuro-Oncology]
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FMR1/circCHAF1A/miR-211-5p/HOXC8 Feedback Loop Regulates Proliferation and Tumorigenesis via MDM2-Dependent p53 Signaling in GSCs

The novel feedback loop among FMR1, circRNA-CHAF1A (circCHAF1A), miR-211-5p, and HOXC8 in glioma stem cells (GSCs) could facilitate the proliferation and tumorigenesis of glioma and GSCs
[Oncogene]
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CD109-GP130 Interaction Drives Glioblastoma Stem Cell Plasticity and Chemoresistance through STAT3 Activity

Researchers reported CD109/STAT3 axis as crucial for the maintenance of stemness and tumorigenicity of glioma stem cells and as a mediator of chemoresistance.
[JCI Insight]
Filppu, P., Ramanathan, J. T., Granberg, K. J., Gucciardo, E., Haapasalo, H., Lehti, K., Nykter, M., Joncour, V. L., & Laakkonen, P. (2021). CD109-GP130 interaction drives glioblastoma stem cell plasticity and chemoresistance through STAT3 activity. JCI Insight, 6(9). https://doi.org/10.1172/jci.insight.141486 Cite
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Elevated Asparagine Biosynthesis Drives Brain Tumor Stem Cell Metabolic Plasticity and Resistance to Oxidative Stress

Researchers showed significant metabolic alterations occur in gliomas when perturbing the expression of asparagine synthetase, which is not merely restricted to amino acid homeostasis.
[Molecular Cancer Research]
Thomas, T. M., Miyaguchi, K., Edwards, L. A., Wang, H., Wollebo, H., Aiguo, L., Murali, R., Wang, Y., Braas, D., Michael, J. S., Andres, A., Zhang, M., Khalili, K., Gottlieb, R. A., Perez, J. M., & Yu, J. S. (2021). Elevated Asparagine Biosynthesis Drives Brain Tumor Stem Cell Metabolic Plasticity and Resistance to Oxidative Stress. Molecular Cancer Research. https://doi.org/10.1158/1541-7786.MCR-20-0086 Cite
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The White Matter Is a Pro-Differentiative Niche for Glioblastoma

Investigators identified the white matter as a differentiative niche for glioblastomas with oligodendrocyte lineage competency.
[Nature Communications]
Brooks, L. J., Clements, M. P., Burden, J. J., Kocher, D., Richards, L., Devesa, S. C., Zakka, L., Woodberry, M., Ellis, M., Jaunmuktane, Z., Brandner, S., Morrison, G., Pollard, S. M., Dirks, P. B., Marguerat, S., & Parrinello, S. (2021). The white matter is a pro-differentiative niche for glioblastoma. Nature Communications, 12(1), 2184. https://doi.org/10.1038/s41467-021-22225-w Cite
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CDK8 Maintains Stemness and Tumorigenicity of Glioma Stem Cells by Regulating the C-MYC Pathway

Investigators demonstrated how cyclin-dependent kinase 8 (CDK8) played an essential role in maintaining stemness and tumorigenicity in glioma stem cells.
[Oncogene]
Fukasawa, K., Kadota, T., Horie, T., Tokumura, K., Terada, R., Kitaguchi, Y., Park, G., Ochiai, S., Iwahashi, S., Okayama, Y., Hiraiwa, M., Yamada, T., Iezaki, T., Kaneda, K., Yamamoto, M., Kitao, T., Shirahase, H., Hazawa, M., Wong, R. W., … Hinoi, E. (2021). CDK8 maintains stemness and tumorigenicity of glioma stem cells by regulating the c-MYC pathway. Oncogene, 1–13. https://doi.org/10.1038/s41388-021-01745-1 Cite
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Rewiring of Purine Metabolism in Response to Acidosis Stress in Glioma Stem Cells

Researchers cultured glioma stem cells at pH 6.8 and pH 7.4 and found that cells cultured in low pH exhibited increased de novo purine nucleotide biosynthesis activity.
[Cell Death & Disease]
Xu, X., Wang, L., Zang, Q., Li, S., Li, L., Wang, Z., He, J., Qiang, B., Han, W., Zhang, R., Peng, X., & Abliz, Z. (2021). Rewiring of purine metabolism in response to acidosis stress in glioma stem cells. Cell Death & Disease, 12(3), 1–12. https://doi.org/10.1038/s41419-021-03543-9 Cite
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Circular RNA-Encoded Oncogenic E-Cadherin Variant Promotes Glioblastoma Tumorigenicity through Activation of EGFR–STAT3 Signaling

The authors report an activation mechanism of EGFR signaling in glioblastoma (GBM) by a secretory E-cadherin protein variant (C-E-Cad) encoded by a circular E-cadherin RNA through multiple-round open reading frame translation. C-E-Cad variant was overexpressed in GBM and promoted glioma stem cell tumorigenicity.
[Nature Cell Biology]
Gao, X., Xia, X., Li, F., Zhang, M., Zhou, H., Wu, X., Zhong, J., Zhao, Z., Zhao, K., Liu, D., Xiao, F., Xu, Q., Jiang, T., Li, B., Cheng, S.-Y., & Zhang, N. (2021). Circular RNA-encoded oncogenic E-cadherin variant promotes glioblastoma tumorigenicity through activation of EGFR–STAT3 signalling. Nature Cell Biology, 1–14. https://doi.org/10.1038/s41556-021-00639-4 Cite
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Glioma Stem Cells as Immunotherapeutic Targets: Advancements and Challenges

Scientists discuss recent advances in glioblastoma treatment specifically focused on targeting of glioma stem cells as well as their potential integration into current clinical pathways and trials.
[Frontiers in Oncology]
Piper, K., DePledge, L., Karsy, M., & Cobbs, C. (2021). Glioma Stem Cells as Immunotherapeutic Targets: Advancements and Challenges. Frontiers in Oncology, 11. https://doi.org/10.3389/fonc.2021.615704 Cite
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Regulatory T Cells Promote Glioma Cell Stemness through TGF-β–NF-κB–IL6–STAT3 Signaling

Mechanistic investigations indicated that TGF-β acted on cancer cells to induce the core cancer stem cell-related genes CD133, SOX2, NESTIN, MUSASHI1 and ALDH1A expression and spheres formation via NF-κB–IL6–STAT3 signaling pathway, resulting in the increased cancer stemness and tumorigenic potential.
[Cancer Immunology Immunotherapy]
Regulatory T cells promote glioma cell stemness through TGF-β–NF-κB–IL6–STAT3 signaling | SpringerLink. (n.d.). Retrieved February 17, 2021, from https://link.springer.com/article/10.1007%2Fs00262-021-02872-0 Cite
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SOX1 Is a Backup Gene for Brain Neurons and Glioma Stem Cell Protection and Proliferation

The authors collate the most important discoveries relating to the neuroprotective effects of SOX1 in brain cancer and propose hypothesis worthy of SOX1’s role in the survival of senescent neuronal cells, its roles in fibroblast cell proliferation, and cell fate for neuroprotection, and the discharge of electrical impulses for homeostasis.
[Molecular Neurobiology]
Kanwore, K., Guo, X., Abdulrahman, A. A., Kambey, P. A., Nadeem, I., & Gao, D. (2021). SOX1 Is a Backup Gene for Brain Neurons and Glioma Stem Cell Protection and Proliferation. Molecular Neurobiology. https://doi.org/10.1007/s12035-020-02240-6 Cite
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