WNT signaling, the development of the sympathoadrenal–paraganglionic system and neuroblastoma

Becker, Jürgen; Wilting, Jörg

doi:10.1007/s00018-017-2685-8

Cited by 32 publications

(37 citation statements)

References 117 publications

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“…In addition, Wnt signaling regulates melanogenesis by stabilization and signaling through Mitf 59 . While a role for Wnt signaling in neuroblast differentiation has been described 43,63 , it has diverse functions in cell proliferation, polarity and migration, so its role in neuroblastoma is likely complex 63 . Nevertheless, the finding here, show that loss of Casp2 affects several components regulating the Wnt signaling pathway in neuroblastoma, that could impact neuronal differentiation and possibly neuroblastoma onset in Th-MYCN/Casp2 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome profiling of caspase-2 deficient EμMyc and Th-MYCN mouse tumors identifies distinct putative roles for caspase-2 in neuronal differentiation and immune signaling

et al. 2019

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Caspase-2 is a highly conserved cysteine protease with roles in apoptosis and tumor suppression. Our recent findings have also demonstrated that the tumor suppression function of caspase-2 is context specific. In particular, while caspase-2 deficiency augments lymphoma development in the EμMyc mouse model, it leads to delayed neuroblastoma development in Th-MYCN mice. However, it is unclear how caspase-2 mediates these differential outcomes. Here we utilized RNA sequencing to define the transcriptomic changes caused by caspase-2 (Casp2−/−) deficiency in tumors from EμMyc and Th-MYCN mice. We describe key changes in both lymphoma and neuroblastoma-associated genes and identified differential expression of the EGF-like domain-containing gene, Megf6, in the two tumor types that may contribute to tumor outcome following loss of Casp2. We identified a panel of genes with altered expression in Th-MYCN/Casp2−/− tumors that are strongly associated with neuroblastoma outcome, with roles in melanogenesis, Wnt and Hippo pathway signaling, that also contribute to neuronal differentiation. In contrast, we found that key changes in gene expression in the EμMyc/Casp2−/− tumors, are associated with increased immune signaling and T-cell infiltration previously associated with more aggressive lymphoma progression. In addition, Rap1 signaling pathway was uniquely enriched in Casp2 deficient EμMyc tumors. Our findings suggest that Casp2 deficiency augments immune signaling pathways that may be in turn, enhance lymphomagenesis. Overall, our study has identified new genes and pathways that contribute to the caspase-2 tumor suppressor function and highlight distinct roles for caspase-2 in different tissues.

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Section: Discussionmentioning

confidence: 99%

Transcriptome profiling of caspase-2 deficient EμMyc and Th-MYCN mouse tumors identifies distinct putative roles for caspase-2 in neuronal differentiation and immune signaling

et al. 2019

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“…Early diagnosis of neuroblastoma is difficult, with a high degree of malignancy and easy to metastasis. The cancer mortality rate of neuroblastoma in children is just fall behind leukemia and brain tumors, which accounts for about 11% (Becker & Wilting, 2018). The prognosis of patients with neuroblastoma is quite variant.…”

Section: Introductionmentioning

confidence: 99%

A prognostic nomogram for neuroblastoma in children

Meng

2019

PeerJ

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Introduction Neuroblastoma is one of the most common extracranial solid tumors in children, which accounts for about 7–10% in children’s tumors. The prognosis group of patients with neuroblastoma could not only improve the efficacy of high-risk patients, but also reduce the effects of drug complications for surviving patients. Material and Methods Patients diagnosed with neuroblastoma between 1986 and 2012 were selected form the TARGET database. The nomogram was built with potential risk factors based on COX regression analysis. The precision of the 3-year and 5-year survival of the nomograms was evaluated by the area under receiver operating characteristic (ROC) curve (AUC). Results A total of 757 child neuroblastoma patients were selected from the TARGET database. Univariate analysis showed that age of diagnosis (>520 day), race of American Indian or Alaska Native, stage 4 in International Neuroblastoma Staging System (INSS), MYCN status, DNA ploidy, and high mitosis-karyorrhexis index were associated with overall survival (OS). Multivariate analysis showed age of diagnosis (>520 day), stage 4 in INSS and DNA ploidy were independent risk factors of OS. The concordance index (C-index) of the nomogram was 0.704 (95% CI [0.686–0.722]) in the training cohort while the C-index in the validation cohort was 0.672 (95% CI [0.644–0.700]). AUC values of ROC curves for 3-year OS and 5-year OS in the training cohort were 0.732 and 0.772, respectively. The nomogram performed better compared with INSS staging system, tumor histology and children’s oncology group (COG) risk group with C-indexes of 0.662 (95% CI [0.648–0.676]), 0.637 (95% CI [0.622–0.652]) and 0.651 (95% CI [0.637–0.665]), respectively. Conclusions The nomogram showed stronger predictive power than the INSS staging system, tumor histology and COG risk group. Precise estimates of the prognosis of childhood neuroblastoma might help doctors make better treatment decisions.

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“…The Wnt protein is a secreted glycoprotein containing a signal peptide and 23 or 24 conserved cysteine residues [ 38 – 40 ]. Wnt signaling pathway affects cell differentiation, proliferation, maturation, and viability [ 41 – 43 ].…”

Section: Discussionmentioning

confidence: 99%

Alleviation by Mahuang Fuzi and Shenzhuo Decoction in High Glucose‐Induced Podocyte Injury by Inhibiting the Activation of Wnt/β‐Catenin Signaling Pathway, Resulting in Activation of Podocyte Autophagy

Dai

Liu

Qiu

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Background. Organ fibrosis is a common endpoint of a variety of diseases. Many studies have shown that the pathogenesis of diabetic kidney disease (DKD) is related to the excessive activation of the Wnt/β-catenin signaling pathway on podocytes, so the treatment of DKD starts from this signaling pathway. At the same time, DKD, as a metabolic disease, has many connections related to podocyte autophagy. Objectives. We experimented the effects of Mahuang Fuzi and Shenzhuo decoction (MFSD) which is the combination of Mahuang Fuzi decoction and Shenzhuo decoction in traditional Chinese medicine compounds used “The Golden Chamber” in high glucose-induced podocytes, determined whether this effect was related to Wnt/β-catenin signaling pathway, and further investigated the relationship between this effect and autophagy. Methods. The mice podocytes were stimulated by using 30 mmol/L of high glucose and serum containing MFSD or Wnt/β-catenin signaling pathway inhibitor DKK1 (100 ng/ml) was used to intervene podocytes before high glucose stimulation. Podocyte injury-related proteins, Wnt/β-catenin signaling pathway-related proteins, and autophagy-related proteins were detected by using western blotting and immunofluorescence analysis. Results. Our results showed that DKK1 and MFSD treatment significantly upregulated the protein expressions of nephrin, podocin, podocalyxin, and podoplanin in high glucose-induced podocytes and downregulated the β-catenin protein expression. Furthermore, the protein expressions of beclin1, LC3B, and P62 were also significantly increased in high glucose-induced podocytes. Conclusion. Our experiments confirmed that the destruction of podocytes in DKD is related to the excessive activation of Wnt/β-catenin signaling pathway and the inhibition of autophagy after activation. MFSD treatment can inhibit the activation of Wnt/β-catenin signaling pathway in podocytes stimulated by high glucose and helpful in reducing the podocyte injury. This protective mechanism can be related to the enhancement of podocyte autophagy by MFSD treatment.

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WNT signaling, the development of the sympathoadrenal–paraganglionic system and neuroblastoma

Cited by 32 publications

References 117 publications

Transcriptome profiling of caspase-2 deficient EμMyc and Th-MYCN mouse tumors identifies distinct putative roles for caspase-2 in neuronal differentiation and immune signaling

Transcriptome profiling of caspase-2 deficient EμMyc and Th-MYCN mouse tumors identifies distinct putative roles for caspase-2 in neuronal differentiation and immune signaling

A prognostic nomogram for neuroblastoma in children

Alleviation by Mahuang Fuzi and Shenzhuo Decoction in High Glucose‐Induced Podocyte Injury by Inhibiting the Activation of Wnt/β‐Catenin Signaling Pathway, Resulting in Activation of Podocyte Autophagy

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