Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurofibromatosis 2 (NF2) is an inherited cancer syndrome in which affected individuals develop nervous system tumors, including schwannomas, meningiomas, and ependymomas. The NF2 protein merlin (or schwannomin) is a member of the Band 4.1 superfamily of proteins, which serve as linkers between transmembrane proteins and the actin cytoskeleton. In addition to mutational inactivation of the NF2 gene in NF2-associated tumors, mutations and loss of merlin expression have also been reported in other types of cancers. In the present study, we show that merlin expression is dramatically reduced in human malignant gliomas and that reexpression of functional merlin dramatically inhibits both subcutaneous and intracranial growth of human glioma cells in mice. We further show that merlin reexpression inhibits glioma cell proliferation and promotes apoptosis in vivo. Using microarray analysis, we identify altered expression of specific molecules that play key roles in cell proliferation, survival, and motility. These merlin-induced changes of gene expression were confirmed by real-time quantitative PCR, Western blotting, and functional assays. These results indicate that reexpression of merlin correlates with activation of mammalian sterile 20-like 1/2-large tumor suppressor 2 signaling pathway and inhibition of canonical and noncanonical Wnt signals. Collectively, our results show that merlin is a potent inhibitor of high-grade human glioma.
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PMID:Merlin is a potent inhibitor of glioma growth. 1863 26

It has been well established that mammalian sterile 20-like 1 (MST1) functions as a suppressor via regulating cell progression in many tumors. However, the molecular mechanism of MST1 on regulating glioma progression remains unclear. Here, we discovered that MST1 was robustly down-regulated in glioma tissues and cells. Functional analysis showed that over-expression of MST1 downregulated viability and colony formation and promoted apoptosis of glioma cells. Our results also identified that MST1 positively regulated expression of SIRT6 (Sirtuin 6) via transcriptional factor FOXO3a (Forkhead box O3a). Furthermore, the functional role of MST1 in glioma cell viability (or apoptosis) were significantly reversed after knocking down of SIRT6. Our research indicates that MST1 is a potential biomarker for the prognosis and diagnosis of glioma and provides new direction on the molecular mechanism of glioma progression and development.
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PMID:MST1 suppresses viability and promotes apoptosis of glioma cells via upregulating SIRT6 expression. 3132 52