Abstract
The Wnt signaling pathway is necessary for the development of the central nervous system and is associated with tumorigenesis in various cancers. However, the mechanism of the Wnt signaling pathway in glioma cells has yet to be elucidated. Small-molecule Wnt modulators such as ICG-001 and AZD2858 were used to inhibit and stimulate the Wnt/β-catenin signaling pathway. Techniques including cell proliferation assay, colony formation assay, Matrigel cell invasion assay, cell cycle assay and Genechip microarray were used. Gene Ontology Enrichment Analysis and Gene Set Enrichment Analysis have enriched many biological processes and signaling pathways. Both the inhibiting and stimulating Wnt/β-catenin signaling pathways could influence the cell cycle, moreover, reduce the proliferation and survival of U87 glioma cells. However, Affymetrix expression microarray indicated that biological processes and networks of signaling pathways between stimulating and inhibiting the Wnt/β-catenin signaling pathway largely differ. We propose that Wnt/β-catenin signaling pathway might prove to be a valuable therapeutic target for glioma.
Highlights
The Wnt/β-catenin pathway is a highly conserved pathway that contains Wnt proteins, Frizzled receptor families, low-density lipoprotein-related protein receptors, cytoplasmic proteins, such as Dishevelled, Axin, glycogensynthase kinase 3 (GSK3) glycoproteins, APC, and transcription factors such as β-catenin, T-cell factor/lymphoid enhancer factor (TCF/LEF) [1,2]
Immunocytochemistry (ICC) results indicated that the neural progenitor marker NESTIN, post-mitotic neuron marker TuJ 1, and glial cell marker glial fibrillary acidic protein (GFAP) were expressed in U87 glioma cells (Fig 1)
Cell death was markedly increased in ICG001-treated cells; the enrichment of the single-organism cellular process, singleorganism process, and cellular component organization in AZD2858-treated cells was higher than that in ICG-001 treated cells. These findings suggested that the reduced cell population in both groups might dominate by different biological processes
Summary
The Wnt/β-catenin pathway is a highly conserved pathway that contains Wnt proteins, Frizzled receptor families, low-density lipoprotein-related protein receptors, cytoplasmic proteins, such as Dishevelled, Axin, glycogensynthase kinase 3 (GSK3) glycoproteins, APC, and transcription factors such as β-catenin, T-cell factor/lymphoid enhancer factor (TCF/LEF) [1,2]. This pathway is one of the well-established signaling pathways during tumorigenesis and plays an important role in the development of the central nervous system.
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