Role of Wnt5a in the proliferation of human glioblastoma cells

Yu, Jian; Jun, Eun Sook; Jung, Jin Kyo; Suh, Su Young; Han, Jin Young; Kim, Jee Yeon; Jung, Jin Sup

doi:10.1016/j.canlet.2007.07.011

Cited by 96 publications

(85 citation statements)

References 26 publications

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“…It has been shown that Wnt5a is overexpressed in high-grade gliomas, but the role for Wnt5a in regulating proliferation and migration in gliomas has only been demonstrated, in a few cell lines, in vitro (23)(24)(25)(26)(27). Here, we explore whether Wnt5a can function as a master regulator of the invasive capacity of hGBMs.…”

Section: Introductionmentioning

confidence: 94%

Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

et al. 2017

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Brain invasion by glioblastoma determines prognosis, recurrence, and lethality in patients, but no master factor coordinating the invasive properties of glioblastoma has been identified. Here we report evidence favoring such a role for the noncanonical WNT family member Wnt5a. We found the most invasive gliomas to be characterized by Wnt5a overexpression, which correlated with poor prognosis and also discriminated infiltrating mesenchymal glioblastoma from poorly motile proneural and classical glioblastoma. Indeed, Wnt5a overexpression associated with tumor-promoting stem-like characteristics (TPC) in defining the character of highly infiltrating mesenchymal glioblastoma cells (Wnt5a High ). Inhibiting Wnt5a in mesenchymal glioblastoma TPC suppressed their infiltrating capability. Conversely, enforcing high levels of Wnt5a activated an infiltrative, mesenchymal-like program in classical glioblastoma TPC and Wnt5aLow mesenchymal TPC. In intracranial mouse xenograft models of glioblastoma, inhibiting Wnt5a activity blocked brain invasion and increased host survival. Overall, our results highlight Wnt5a as a master regulator of brain invasion, specifically TPC, and they provide a therapeutic rationale to target it in patients with glioblastoma. Cancer Res; 77(4); 996-1007. Ó2016 AACR.

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Section: Introductionmentioning

confidence: 94%

Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

et al. 2017

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“…Notably, Wnt5a is the most upregulated Wnt member in glioma cells and tissues, which promotes cell proliferation, migration and tumorigenesis both in vitro and in vivo (15,35). In addition, Wnt5a is associated with the antagonization of the canonical Wnt/β-catenin activity in mammalian cells and Xenopus embryos (36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

“…For example, the upregulation of Wnt5a may enhance, whilst the downregulation may reduce, the proliferation and tumorigenesis of GBM-05 and U87MG cell lines (35). The knockdown of Wnt5a suppresses the migration, invasion and infiltrative capacity of glioma cells primarily via a matrix metallopeptidase-2-dependent mechanism (15).…”

Section: Discussionmentioning

confidence: 99%

Expression profile and clinical significance of Wnt signaling in human gliomas

Zhang

Geng

et al. 2017

Oncol Lett

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Abstract. Wnt signaling has been identified as a critical regulator of human tumor development in vitro. However, there remains a lack of studies systematically examining the expression pattern and clinical relevance of the core molecules of Wnt signaling in glioma tissues. In the present study, it was identified that the mRNA expression levels of Wnt3a and 5a, and their receptors frizzled 2, 6 and 7 increased, whereas Wnt7b was markedly decreased in glioma relative to non-tumor tissue. The mRNA levels of β-catenin, adenomatous polyposis coli gene product, glycogen synthase kinase 3β (GSK3β) and AXIN1 and its target genes cyclin D1 and AXIN2 did not differ. Similarly, the protein levels of Wnt2b, 3a and 5a were increased in gliomas, while β-catenin, GSK3β and cyclin D1 were not. Furthermore, based on data from the R2: Genomics Analysis and Visualization Platform, the expression of Wnt2b and 5a, and frizzled 2, 6 and 7 were highly associated with the prognosis of patients with glioma. Taken together, the results of the present study demonstrate that β-catenin is not upregulated in gliomas and that the Wnt signaling pathway may promote glioma development via noncanonical or alternative pathways.

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“…An increased Wnt5a expression was detected during proliferation in U87MG cell line. On the contrary, Wnt5a suppression due to RNA interference reduces proliferation of this culture and decreases tumorigenicity іn vivo [60]. …”

Section: Therapeutic Approaches To the Target Impacts On The Cancer Smentioning

confidence: 96%

Brain tumor stem cells: phenotypic characterization and directed therapeutic approaches

Belska¹,

Lisianyi²

2015

JCOT

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The review presents the current conceptions of the origin, methods of isolation and phenotypic characterization of the brain tumor stem cells. Phenotypic similarity in molecular markers between cancer and neural stem cells is shown. Therapeutic approaches of impact on the brain tumor stem cells and on the intracellular signaling pathways of cancer stem cells are described. KEYWORDS: brain tumor stem cells, neural stem cells, malignant gliomas, CD133, nestinnumber of CSCs in different types of cancer varies from 1 % to 20 % and even more in some cases. The brain tumor stem cells (BTSCs) possess an indefinite capacity for self-maintenance, tumor generation during ortotopic implantation, genetic disorders and formation of cancer cells [6]. BTSCs possess great capacity for invasion, stimulate formation of the blood vessels and initiate cell migration [2,3]. Apart from this, they are involved in the stimulation of cancerogenesis: there appear more and more corroborations that these cells promote cancer progression [7] and metastasis [8]. This type of cells is responsible for chemo-and radio resistance, post-surgery and radiotherapy relapse.

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Role of Wnt5a in the proliferation of human glioblastoma cells

Cited by 96 publications

References 26 publications

Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

Expression profile and clinical significance of Wnt signaling in human gliomas

Brain tumor stem cells: phenotypic characterization and directed therapeutic approaches

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