SPOPL induces tumorigenicity and stemness in glioma stem cells by activating Notch signaling. 2023

Tianyu Hu, and Ruoheng Xuan, and Erqiao Han, and Lingshan Cai, and Zhibo Xia
Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

OBJECTIVE Recent studies have increasingly shown that glioma stem cells (GSCs) are extremely important for developing and treating glioblastoma multiforme (GBM). The Broad-complex, Tram-track, and Bric-a-brac protein family is functionally related to a variety of tumor stem cells, and the role of SPOPL as a member of this family in GSCs deserves to be investigated. METHODS To investigate the expression of SPOPL in GSCs and its impact on the prognosis of GBM patients by using clinical specimens, patient-derived primary GSCs and public databases. In vivo and in vitro, the effect of SPOPL on the proliferation, self-renewal, and differentiation ability of GSCs was explored. Probing the mechanism by which SPOPL affects the biological function of GSCs using RNA sequencing (RNA-seq) and rescue experiments. RESULTS The expression of SPOPL was significantly upregulated in GSCs and GBM, and patients with high SPOPL expression had a poorer prognosis. SPOPL enhanced the proliferation and self-renewal ability of GSCs and enhanced the tumorigenicity of GSCs. The Notch signaling pathway was significantly inhibited in SPOPL knockdown GSCs. Activation or inhibition of the Notch signaling pathway rescued changes in the biological function of GSCs caused by altered SPOPL expression. CONCLUSIONS SPOPL can be used as a potential prognostic biomarker for GBM in clinical work and promotes the proliferation and stemness of GSCs by activating the Notch signaling pathway, which may be a potential molecule for targeting GSCs to treat GBM.

UI MeSH Term Description Entries
D001932 Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D005909 Glioblastoma A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. Astrocytoma, Grade IV,Giant Cell Glioblastoma,Glioblastoma Multiforme,Astrocytomas, Grade IV,Giant Cell Glioblastomas,Glioblastoma, Giant Cell,Glioblastomas,Glioblastomas, Giant Cell,Grade IV Astrocytoma,Grade IV Astrocytomas
D005910 Glioma Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21) Glial Cell Tumors,Malignant Glioma,Mixed Glioma,Glial Cell Tumor,Glioma, Malignant,Glioma, Mixed,Gliomas,Gliomas, Malignant,Gliomas, Mixed,Malignant Gliomas,Mixed Gliomas,Tumor, Glial Cell,Tumors, Glial Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014411 Neoplastic Stem Cells Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS. Cancer Stem Cells,Colony-Forming Units, Neoplastic,Stem Cells, Neoplastic,Tumor Stem Cells,Neoplastic Colony-Forming Units,Tumor Initiating Cells,Cancer Stem Cell,Cell, Cancer Stem,Cell, Neoplastic Stem,Cell, Tumor Initiating,Cell, Tumor Stem,Cells, Cancer Stem,Cells, Neoplastic Stem,Cells, Tumor Initiating,Cells, Tumor Stem,Colony Forming Units, Neoplastic,Colony-Forming Unit, Neoplastic,Initiating Cell, Tumor,Initiating Cells, Tumor,Neoplastic Colony Forming Units,Neoplastic Colony-Forming Unit,Neoplastic Stem Cell,Stem Cell, Cancer,Stem Cell, Neoplastic,Stem Cell, Tumor,Stem Cells, Cancer,Stem Cells, Tumor,Tumor Initiating Cell,Tumor Stem Cell,Unit, Neoplastic Colony-Forming,Units, Neoplastic Colony-Forming
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular

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