The role of the Wnt canonical signaling in neurodegenerative diseases

Libro, Rosaliana; Bramantı, Placido; Mazzon, Emanuela

doi:10.1016/j.lfs.2016.06.024

Cited by 129 publications

(83 citation statements)

References 155 publications

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“…Aberrant activation of Wnt/β-catenin signaling pathway is associated with a variety of pathological alterations, including cancer, metabolic disorder and neurodegenerative diseases (Libro et al, 2016; Ma and Hottiger, 2016). Some studies have demonstrated that Wnt/β-catenin signaling pathway was involved in the properties of CSCs, and was closely correlated with EMT (Reya and Clevers, 2005; Ghahhari and Babashah, 2015; Zhang et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Fentanyl Promotes Breast Cancer Cell Stemness and Epithelial-Mesenchymal Transition by Upregulating α1, 6-Fucosylation via Wnt/β-Catenin Signaling Pathway

Yang

Jin

et al. 2017

Front. Physiol.

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Cancer pain is a common and severe complication of human breast cancer, and relieving pain is fundamental strategy in the treatment. Fentanyl, as an opioid analgesic, is widely used in breast cancer patients. However, little is known about its effects on stemness and epithelial-mesenchymal transition (EMT) of breast cancer cells. Aberrant protein glycosylation is involved in cancer malignancy. The α1, 6-fucosylation is an important type of glycosylation, and the elevated α1, 6-fucosylation catalyzed by fucosyltransferase VIII (FUT8) is found in many tumors. However, whether 1, 6-fucosylation is involved in regulating stemness and EMT, and stimulated by fentanyl is not clear. In this study, we found that fentanyl induced stemness and EMT in MCF-7 and MDA-MB-231 breast cancer cells by analysis of sphere formation, expression of stemness markers (Sox2, Oct4) and EMT markers (N-cadherin, E-cadherin and Vimentin). Results also showed that fentanyl upregulated FUT8 gene and protein expression by qPCR, Western blot and immunofluorescent staining, as well as α1, 6-fucosylation level by Lectin blot and Lectin fluorescent staining. Furthermore, decreased or blocked α1, 6-fucosylation by FUT8 siRNA transfection or LCA Lectin blockage reduced stemness and EMT. Additionally, fentanyl activated the key molecules and target genes in Wnt/β-catenin signaling pathway. LGK-974 (an inhibitor of Wnt ligands) suppressed fentanyl-mediated upregulation of α1, 6-fucosylation, stemness and EMT. The results of tumor xenograft demonstrated that fentanyl enhanced tumor growth, α1, 6-fucosylation, stemness and EMT. Taken together, our study reveals that fentanyl upregulated FUT8 expression, which increased α1, 6-fucosylation level through activation of Wnt/β-catenin signaling pathway, thereby, induce stemness and EMT of breast cancer cells. This study suggest a potential side effect of fentanyl in the treatment of cancer, which may guide the safety of fentanyl in the clinical application.

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Section: Discussionmentioning

confidence: 99%

Fentanyl Promotes Breast Cancer Cell Stemness and Epithelial-Mesenchymal Transition by Upregulating α1, 6-Fucosylation via Wnt/β-Catenin Signaling Pathway

Yang

Jin

et al. 2017

Front. Physiol.

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“…However, alterations of Wnt canonical signaling pathway functionally lead to diverse neuropathologies and neurodevelopmental dysfunctions, such as altered synaptic plasticity, that have been reviewed by Inestrosa et al (2015) and Tang et al (2014) . Indeed, Wnt signaling pathway dysfunctions are involved in the etiopathogenesis of various neurological diseases such as chronic pain, cerebral ischemia, Huntington disease, amyotrophic lateral sclerosis and other neurodegenerative pathologies . Wnt alterations in schizophrenia could be through roles of this signaling pathway in neuronal migration, survival, and/or apoptosis .…”

Section: Discussionmentioning

confidence: 99%

Dental and extra‐oral clinical features in 41 patients with WNT10A gene mutations: A multicentric genotype–phenotype study

et al. 2017

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WNT10A gene encodes a canonical wingless pathway signaling molecule involved in cell fate specification as well as morphogenetic patterning of the developing ectoderm, nervous system, skeleton, and tooth. In patients, WNT10A mutations are responsible for ectodermal-derived pathologies including isolated hypo-oligodontia, tricho-odonto-onycho-dermal dysplasia and Schöpf-Schulz-Passarge syndrome (SSPS). Here we describe the dental, ectodermal, and extra-ectodermal phenotypic features of a cohort of 41 patients from 32 unrelated families. Correlations with WNT10A molecular status (heterozygous carrier, compound heterozygous, homozygous) and patient's phenotypes were performed. Mild to severe oligodontia was observed in all patients bearing biallelic WNT10A mutations. However, patients with compound heterozygous mutations presented no significant difference in phenotypes compared with homozygous individuals. Anomalies in tooth morphology were frequently observed with heterozygous patients displaying hypodontia. No signs of SSPS, especially eyelids cysts, were detected in our cohort. Interestingly, extra-ectodermal signs consisted of skeletal, neurological and vascular anomalies, the latter suggesting a wider phenotypic spectrum associated with WNT10A mutations. Indeed, the Wnt pathway plays a crucial role in skeletal development, lipid metabolism, and neurogenesis, potentially explaining patient's clinical manifestations.

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“…This is in agreement with (Guo et al 2017), who reported that pERK activates the Wnt canonical pathway in cancer cells. Moreover, (Libro et al 2016) showed that Wnt-βcatenin signal perturbations are associated with cell death in the CNS. Therefore, pERK expression in the radial glia fibers is required to maintain the Wnt signal in TML, which is necessary for the survival of VL Th nuclei.…”

Section: Discussionmentioning

confidence: 99%

Radial glia fibers translate Fgf8 morphogenetic signals to generate a thalamic nuclear complex protomap in the mantle layer

2018

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Thalamic neurons are distributed between different nuclear groups of the thalamic multinuclear complex; they develop topologically ordered specific projections that convey information on voluntary motor programs and sensory modalities to functional areas in the cerebral cortex. Since thalamic neurons present a homogeneous morphology, their functional specificity is derived from their afferent and efferent connectivity. Adequate development of thalamic afferent and efferent connections depends on guide signals that bind receptors in nuclear neuropils and axonal growth cones, respectively. These are finally regulated by regionalization processes in the thalamic neurons, codifying topological information. In this work, we studied the role of Fgf8 morphogenetic signaling in establishing the molecular thalamic protomap, which was revealed by Igsf21, Pde10a and Btbd3 gene expression in the thalamic mantle layer. Fgf8 signaling activity was evidenced by pERK expression in radial glia cells and fibers, which may represent a scaffold that translates neuroepithelial positional information to the mantle layer. In this work, we describe the fact that Fgf8-hypomorphic mice did not express pERK in radial glia cells and fibers and presented disorganized thalamic regionalization, increasing neuronal death in the ventro-lateral thalamus and strong disruption of thalamocortical projections. In conclusion, Fgf8 encodes the positional information required for thalamic nuclear regionalization and the development of thalamocortical projections.Electronic supplementary materialThe online version of this article (10.1007/s00429-018-1794-y) contains supplementary material, which is available to authorized users.

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The role of the Wnt canonical signaling in neurodegenerative diseases

Cited by 129 publications

References 155 publications

Fentanyl Promotes Breast Cancer Cell Stemness and Epithelial-Mesenchymal Transition by Upregulating α1, 6-Fucosylation via Wnt/β-Catenin Signaling Pathway

Fentanyl Promotes Breast Cancer Cell Stemness and Epithelial-Mesenchymal Transition by Upregulating α1, 6-Fucosylation via Wnt/β-Catenin Signaling Pathway

Dental and extra‐oral clinical features in 41 patients with WNT10A gene mutations: A multicentric genotype–phenotype study

Radial glia fibers translate Fgf8 morphogenetic signals to generate a thalamic nuclear complex protomap in the mantle layer

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