Sox11 Prevents Tumorigenesis of Glioma-Initiating Cells by Inducing Neuronal Differentiation

Hide, Takuichiro; Nakatani, Yuka; Nakamura, Hideo; Kuratsu, Jun Ichi; Kondo, Toru

doi:10.1158/0008-5472.can-09-2006

Cited by 107 publications

(142 citation statements)

References 30 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…Inactivation of PTEN leads to increased expression of c-Myc that is critical for maintaining GSC proliferation and self-renewal, suggesting promoting PTEN function may suppress the "stemness" of GSCs and induce GSC differentiation. In another study, Sox11 has been shown to induce GSC differentiation (Hide et al, 2009). Overexpression of Sox11 inhibits tumorigenic potential of GSCs by promoting neuronal differentiation.…”

Section: Differentiation Of Glioblastoma Stem Cellsmentioning

confidence: 96%

Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

et al. 2010

View full text Add to dashboard Cite

Glioblastomas (GBMs) are highly lethal primary brain tumors. Despite current therapeutic advances in other solid cancers, the treatment of these malignant gliomas remains essentially palliative. GBMs are extremely resistant to conventional radiation and chemotherapies. We and others have demonstrated that a highly tumorigenic subpopulation of cancer cells called GBM stem cells (GSCs) promotes therapeutic resistance. We also found that GSCs stimulate tumor angiogenesis by expressing elevated levels of VEGF and contribute to tumor growth, which has been translated into a useful therapeutic strategy in the treatment of recurrent or progressive GBMs. Furthermore, stem cell-like cancer cells (cancer stem cells) have been shown to promote metastasis. Although GBMs rarely metastasize beyond the central nervous system, these highly infiltrative cancers often invade into normal brain tissues preventing surgical resection, and GSCs display an aggressive invasive phenotype. These studies suggest that targeting GSCs may effectively reduce tumor recurrence and significantly improve GBM treatment. Recent studies indicate that cancer stem cells share core signaling pathways with normal somatic or embryonic stem cells, but also display critical distinctions that provide important clues into useful therapeutic targets. In this review, we summarize the current understanding and advances in glioma stem cell research, and discuss potential targeting strategies for future development of anti-GSC therapies.

show abstract

Section: Differentiation Of Glioblastoma Stem Cellsmentioning

confidence: 96%

Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

et al. 2010

View full text Add to dashboard Cite

show abstract

“…14,15 Briefly, NSCs were prepared from embryonic day 14.5 mouse telencephalon and expanded in DMEM/F12 (Wako, Japan) supplemented with chemicals, bFGF (10 ng/mL), and EGF (10 ng/mL) as described previously.…”

Section: Establishment Of Mouse Gic Lines and Cell Culturementioning

confidence: 99%

“…14,15 Briefly, the cells were suspended in 0.3% top agar and layered onto 0.6% bottom agar. After the top agar solidified, culture medium was added and the cells were cultured for 20 d with medium changes every 3 d.…”

Section: Soft Agar Assaymentioning

confidence: 99%

“…14,15 When transplanted into WT mice, 10 times more GICs were used than those in nude mice. For histopathology, the dissected mouse brains were fixed in 4% paraformaldehyde at 4 C overnight, dehydrated and embedded in paraffin.…”

Section: Intracranial Cell Transplantation and Histopathologymentioning

confidence: 99%

“…Using the mouse glioma-initiating cell (GIC) models, 14,15 we addressed how Ecrg4 acts as a tumor suppressor in vivo. Unexpectedly, we found that Ecrg4 from GICs, rather than tumor-surrounding cells, was essential for its tumor-suppressor function.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ecrg4 contributes to the anti-glioma immunosurveillance through type-I interferon signaling

et al. 2016

Self Cite

View full text Add to dashboard Cite

Esophageal cancer-related gene 4 (Ecrg4), a hormone-like peptide, is thought to be a tumor suppressor, however, little is known about the mechanism of how Ecrg4 suppresses tumorigenesis. Here, we show that the ecrg4 null glioma-initiating cell (GIC) line, which was generated from neural stem cells of ecrg4 knockout (KO) mice, effectively formed tumors in the brains of immunocompetent mice, whereas the transplanted ecrg4 wild type-GIC line GIC(C/C) was frequently eliminated. This was caused by host immune system including adaptive T cell responses, since depletion of CD4 C , CD8 C , or NK cells by specific antibodies in vivo recovered tumorigenicity of GIC(C/C). We demonstrate that Ecrg4 fragments, amino acid residues 71-132 and 133-148, which are produced by the proteolitic cleavage, induced the expression of pro-inflammatory cytokines in microglia in vitro. Moreover, blockades of type-I interferon (IFN) signaling in vivo, either depleting IFN-a/b receptor 1 or using stat1 KO mice, abrogated the Ecrg4-dependent antitumor activity. Together, our findings indicate a major antitumor function of Ecrg4 in enhancing host immunity via type-I IFN signaling, and suggest its potential as a clinical candidate for cancer immunotherapy.

show abstract

miR‐221/222 suppression induced by activation of the cAMP/PKA/CREB1 pathway is required for cAMP‐induced bidirectional differentiation of glioma cells

2021

View full text Add to dashboard Cite

Factors that increase cAMP levels can induce lineage‐specific differentiation of glioma cells into astrocyte‐like cells. However, the differentiation pattern and underlying mechanisms remain unclear. Here, we find that cAMP/protein kinase A (PKA)/cAMP responsive element binding protein 1 (CREB1)‐induced miR‐221/222 suppression contributes to the neuron‐like differentiation of gliomas. cAMP agonists selectively induced neuron‐ and astrocyte‐like but not oligodendrocyte‐like differentiation of C6 glioma cells. PKA inhibitors and CREB1 knockout blocked neuron‐like differentiation of glioma cells. cAMP inhibited miR‐221/222 in a PKA/CREB1‐dependent manner. Importantly, both in vitro and in vivo assays demonstrated that transcriptional suppression of miR‐221/222 is required for neuronal differentiation of glioma cells. Our findings suggest that increasing cAMP levels can induce bidirectional differentiation of glioma cells. Furthermore, the miR‐221/222 cluster acts as an epigenetic brake during glioma differentiation.

show abstract

Sox11 Prevents Tumorigenesis of Glioma-Initiating Cells by Inducing Neuronal Differentiation

Cited by 107 publications

References 30 publications

Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

Ecrg4 contributes to the anti-glioma immunosurveillance through type-I interferon signaling

miR‐221/222 suppression induced by activation of the cAMP/PKA/CREB1 pathway is required for cAMP‐induced bidirectional differentiation of glioma cells

Contact Info

Product

Resources

About