Small molecule GSK-3 inhibitors increase neurogenesis of human neural progenitor cells

Lange, Christian; Mix, Eilhard; Frahm, Jana; Glass, Änne; Müller, Jana; Schmitt, Oliver; Schmöle, Anne-Caroline; Klemm, Kristin; Ortinau, Stefanie; Hübner, Rayk; Frech, Moritz J.; Wree, Andreas; Rolfs, Arndt

doi:10.1016/j.neulet.2010.10.076

Cited by 92 publications

(56 citation statements)

References 25 publications

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“…Previous studies highlight the critical role Wnt signaling plays in NSCs, but the nature of the Wnt signals involved remains unclear, with reports of increased and decreased Wnt signaling taking place during differentiation [68,175] and disease [176,177]. Neurogenesis in the hippocampus, where Wnt signaling plays important roles, is gradually lost as we age [178], and this loss is implicated in neurodegenerative diseases [123].…”

Section: Discussionmentioning

confidence: 99%

Canonical and noncanonical Wnt signaling in neural stem/progenitor cells

Bengoa-Vergniory

Kypta

2015

Cell. Mol. Life Sci.

138

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Section: Discussionmentioning

confidence: 99%

Canonical and noncanonical Wnt signaling in neural stem/progenitor cells

Bengoa-Vergniory

Kypta

2015

Cell. Mol. Life Sci.

138

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“…In several previous studies, chemical inhibitors of GSK3 have been used in attempts to define the roles of GSK3 [7][8][9]. To confirm the effect of GSK3 inhibition on the differentiation of NPCs, we used SB216763, an ATP-competitive inhibitor of GSK3 [21].…”

Section: Effects Of Gsk3 Inhibition On the Neuronal Differentiation Omentioning

confidence: 99%

“…In contrast, mutant Drosophila that are defective in the shaggy gene, a GSK3 homologue, show increased neuronal differentiation [6]. The use of GSK3 inhibitors also promotes neuronal differentiation of human NPCs, rat ventral midbrain precursors, and rat neural stem cells [7][8][9]. Due to the conflicting results of these studies, the functions of GSK3 in the differentiation of NPCs and the exact effects of GSK3a and GSK3b still remain elusive.…”

Section: Introductionmentioning

confidence: 99%

GSK3β, But Not GSK3α, Inhibits the Neuronal Differentiation of Neural Progenitor Cells As a Downstream Target of Mammalian Target of Rapamycin Complex1

Ahn

Jang

Choi

et al. 2014

Stem Cells and Development

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“…Identification of molecular pathways essential for CSC self-renewal is critical for designing effective cancer therapeutics. The Wnt signaling pathway is an essential pathway that regulates non-neoplastic stem cells, including cell proliferation, differentiation and migration processes, which have been verified in various stem cells such as embryonic stem cells (9,10), neural progenitor cells (11,12), hematopoietic (13) and cardiovascular stem cells (14). The similarities between normal adult stem cells and CSCs suggest that the signaling pathways involved in somatic stem cell maintenance may also be involved in the regulation of CSCs.…”

Section: Introductionmentioning

confidence: 99%

The Wnt/β-catenin pathway regulates self-renewal of cancer stem-like cells in human gastric cancer

Cai

Zhu

2012

Mol Med Report

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Abstract. Cancer stem cells (CSCs) possess the ability of self-renewal and tumor initiation. Targeting key signaling pathways that are active in CSC self-renewal is one approach to cancer therapy. Abnormal activation of the Wnt/β-catenin pathway has been described in a wide variety of human cancers and in CSCs; however, the role of this pathway in gastric CSCs has not been reported. In our study, we investigated whether the Wnt/β-catenin pathway plays an important role in gastric CSCs. First, we isolated cancer stem-like cells (CSLCs) from the human gastric cancer cell line MKN-45 using tumorsphere cultures. We tested whether tumorsphere cells were CSLCs using the following three criteria: i) We identified that the expression of the CSC marker CD44 was significantly greater in tumorsphere cells compared to adherent cells; ii) compared with adherent cells, the floating tumorsphere cells had greater self-renewing capacity; iii) in vivo xenograft studies showed that tumorsphere cells generate larger tumors than adherent cells at the same number. In addition, we studied the mechanism(s) by which the canonical Wnt signaling pathway acts in CSLCs. Western blotting and real-time PCR showed that the expression levels of β-catenin and c-myc, cyclin d1 and axin 2 were downregulated/upregulated with the inhibition/activation of the Wnt pathway. The pathway blocked by DKK-1 caused a higher reduction in the self-renewing capacity of MKN-45 tumorsphere cells and the pathway activated by lithium chloride improved the self-renewal of CSLCs. In conclusion, our data suggested that the Wnt/β-catenin pathway is essential for the self-renewal of CSLCs in human gastric cancer.

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Small molecule GSK-3 inhibitors increase neurogenesis of human neural progenitor cells

Cited by 92 publications

References 25 publications

Canonical and noncanonical Wnt signaling in neural stem/progenitor cells

Canonical and noncanonical Wnt signaling in neural stem/progenitor cells

GSK3β, But Not GSK3α, Inhibits the Neuronal Differentiation of Neural Progenitor Cells As a Downstream Target of Mammalian Target of Rapamycin Complex1

The Wnt/β-catenin pathway regulates self-renewal of cancer stem-like cells in human gastric cancer

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