Nanog down-regulates the Wnt signaling pathway via β-catenin phosphorylation during epidermal stem cell proliferation and differentiation

Peng, Cheng; Sun, Xuying; Yin, Delong; Xu, Fei; Yang, Kai; Qin, Liang; Dong, Yonghui; Guo, Fengjing; Chen, Anmin; Zhang, Weikai; Huang, Hui

doi:10.1186/2045-3701-5-5

Cited by 10 publications

(10 citation statements)

References 37 publications

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“…Following treatment for 48 h, the expression of MYC was significantly decreased by Rau treatment, which is consistent with Wnt/β-catenin signaling pathway inhibition. Studies have shown that the stem cell-related gene Nanog has the ability to induce β-catenin phosphorylation and enhances its degradation ( 38 ). Therefore, the present study examined the expression of Nanog by western blot analysis.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of pancreatic cancer stem cells by Rauwolfia vomitoria extract

Dong

Chen

2018

Oncol Rep

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The poor treatment outcomes of pancreatic cancer are linked to an enrichment of cancer stem cells (CSCs) in these tumors, which are resistant to chemotherapy and promote metastasis and tumor recurrence. The present study investigated an extract from the root of the medicinal plant Rauwolfia vomitoria (Rau) for its activity against pancreatic CSCs. In vitro tumor spheroid formation and CSC markers were tested, and in vivo tumorigenicity was evaluated in nude mice. Rau inhibited the overall proliferation of human pancreatic cancer cell lines with a 50% inhibitory concentration (IC50) ranging between 125 and 325 µg/ml, and showed limited cytotoxicity towards normal epithelial cells. The pancreatic CSC population, identified using cell surface markers or a tumor spheroid formation assay, was significantly reduced, with an IC50 value of ~100 µg/ml treatment for 48 h and ~27 µg/ml for long-term tumor spheroid formation. The levels of CSC-related gene Nanog and nuclear β-catenin were decreased, suggesting suppression of the Wnt/β-catenin signaling pathway. In vivo, 20 mg/kg of Rau administered five times per week by oral gavage significantly reduced the tumorigenicity of PANC-1 cells in immunocompromised mice. Taken together, these data showed that Rau preferentially inhibited pancreatic cancer stem cells. Further investigation is warranted to examine the potential of Rau as a novel treatment for pancreatic cancer.

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Section: Resultsmentioning

confidence: 99%

Inhibition of pancreatic cancer stem cells by Rauwolfia vomitoria extract

Dong

Chen

2018

Oncol Rep

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“…Studies have shown that a stem cell related gene Nanog can induce β-catenin phosphorylation and therefore enhance its degradation, and consequently inhibit Wnt signaling pathway. 35 We therefore examined the expression of Nanog by Western blot. Nanog was increased at 24 hours of Pao treatment but was decreased at 48 hours of Pao treatment ( Figure 4B ).…”

Section: Resultsmentioning

confidence: 99%

Extract of the Medicinal Plant Pao Pereira Inhibits Pancreatic Cancer Stem-Like Cell In Vitro and In Vivo

Dong

Chen

2018

Integr Cancer Ther

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Pancreatic cancers are enriched with cancer stem-like cells (CSCs), which are resistant to chemotherapies, and responsible for tumor metastasis and recurrence. Here, we investigated the extract of a medicinal plant Pao Pereira (Pao) for its activity against pancreatic CSCs. Pao inhibited overall proliferation of human pancreatic cancer cell lines with IC50 ranging from 125 to 325 μg/mL and had limited cytotoxicity to normal epithelial cells. Pancreatic CSC population, identified using surface markers CD24+ CD44+ EpCam+ or tumor spheroid formation assay, was significantly reduced, with IC50s of ~100 μg/mL for 48 hours treatment, and ~27 μg/mL for long-term treatment. Nuclear β-catenin levels were decreased, suggesting suppression of Wnt/β-catenin signaling pathway. In vivo, Pao at 20 mg/kg, 5 times/week gavage, significantly reduced tumorigenicity of PANC-1 cells in immunocompromised mice, indicating inhibition of CSCs in vivo. Further investigation is warranted in using Pao as a novel treatment targeting pancreatic CSCs.

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“…Thus, our study shows how constitutive heterozygous germline mutations affect early kidney development and provides further insights into the mechanisms underlying the renal developmental abnormalities associated with RCAD and their consequences in postnatal life. In summary, the Hnf1b Sp2/+ mouse model represents a unique clinical/pathological viable model of the human disease and promises to be important in the integrative evaluation, in the context of the whole animal, of the broad facets of this disease, ranging from various developmental abnormalities to kidney, pancreas and liver dysfunctions as well as tumorigenesis ( Yu et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Hnf1b haploinsufficiency differentially affects developmental target genes in a new renal cysts and diabetes mouse model

Niborski

Paces-Fessy

Ricci

et al. 2021

Disease Models &Amp; Mechanisms

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Heterozygous mutations in HNF1B cause the complex syndrome Renal Cysts and Diabetes (RCAD), characterized by developmental abnormalities of the kidneys, genital tracts and pancreas, and a variety of renal, pancreas and liver dysfunctions. The pathogenesis underlying this syndrome remains unclear as mice with heterozygous null mutations have no phenotype, while constitutive/conditional Hnf1b-ablation leads to more severe phenotypes.We generated a novel mouse model carrying an identified human mutation at the intron-2 splice donor-site. Unlike heterozygous previously characterized, heterozygous for the splicing mutation exhibited decreased HNF1B protein levels and bilateral renal cysts from embryonic stage E15, originated from glomeruli, early proximal tubules (PT) and intermediate nephron segments, concurrently with a delayed PT differentiation, hydronephrosis and rare genital tract anomalies.Consistently, mRNA-sequencing showed that most down-regulated genes in embryonic kidneys were primarily expressed in early PTs and Henle's Loop and involved in ion/drug transport, organic acid and lipid metabolic processes, while the expression of previously identified targets upon Hnf1b-ablation, including cystic disease genes was weakly or not affected. Postnatal analyses revealed renal abnormalities, ranging from glomerular cysts to hydronephrosis and rarely multicystic dysplasia. Urinary proteomics uncovered a particular profile predictive of progressive decline in kidney function and fibrosis, and displayed common features with a recently reported urine proteome in a RCAD pediatric cohort. Altogether our results show that HNF1B reduced levels lead to developmental disease phenotypes associated with the deregulation of a subset of its targets. They further suggest that this model represents a unique clinical/pathological viable model of the RCAD disease.

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Nanog down-regulates the Wnt signaling pathway via β-catenin phosphorylation during epidermal stem cell proliferation and differentiation

Cited by 10 publications

References 37 publications

Inhibition of pancreatic cancer stem cells by Rauwolfia vomitoria extract

Inhibition of pancreatic cancer stem cells by Rauwolfia vomitoria extract

Extract of the Medicinal Plant Pao Pereira Inhibits Pancreatic Cancer Stem-Like Cell In Vitro and In Vivo

Hnf1b haploinsufficiency differentially affects developmental target genes in a new renal cysts and diabetes mouse model

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