scholarly journals Is resistant starch protective against colorectal cancer via modulation of the WNT signalling pathway?

2015 ◽  
Vol 74 (3) ◽  
pp. 282-291 ◽  
Author(s):  
Fiona C. Malcomson ◽  
Naomi D. Willis ◽  
John C. Mathers
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Resistant Starch ◽  
Wnt Pathway ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Wnt Signalling Pathway ◽  
Crypt Cell Proliferation ◽  
And Migration ◽  
Epigenetic Modulation

Epidemiological and experimental evidence suggests that non-digestible carbohydrates (NDC) including resistant starch are protective against colorectal cancer. These anti-neoplastic effects are presumed to result from the production of the SCFA, butyrate, by colonic fermentation, which binds to the G-protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes. The WNT pathway is central to the maintenance of homeostasis within the large bowel through regulation of processes such as cell proliferation and migration and is frequently aberrantly hyperactivated in colorectal cancers. Abnormal WNT signalling can lead to irregular crypt cell proliferation that favours a hyperproliferative state. Butyrate has been shown to modulate the WNT pathway positively, affecting functional outcomes such as apoptosis and proliferation. Butyrate's ability to regulate gene expression results from epigenetic mechanisms, including its role as a histone deacetylase inhibitor and through modulating DNA methylation and the expression of microRNA. We conclude that genetic and epigenetic modulation of the WNT signalling pathway may be an important mechanism through which butyrate from fermentation of resistant starch and other NDC exert their chemoprotective effects.

scholarly journals Elevated expression of LGR5 and WNT signalling factors in neuroblastoma cells with acquired drug resistance

2018 ◽  
Author(s):  
Svetlana Myssina ◽  
John Clark-Corrigall ◽  
Martin Michaelis ◽  
Jindrich Cinatl ◽  
Shafiq U. Ahmed ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cell Lines ◽  
Survival Rates ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Solid Cancer ◽  
Acquired Drug Resistance ◽  
Wnt Signalling Pathway ◽  
Elevated Expression

AbstractNeuroblastoma (NB) is the most common paediatric solid cancer with high fatality, relapses and acquired resistance to drug therapy. The clinical challenge NB poses requires new therapeutic approaches to improve survival rates.The WNT signalling pathway is crucial in embryonic development but has also been reported to be dysregulated in glioblastoma, ovarian, breast and colorectal cancer. LGR5 is a receptor which potentiates the WNT/β-catenin signalling pathway, hence contributing to cancer stem cell proliferation and self-renewal. LGR5 has been reported to promote both development and survival of colorectal cancer and glioblastomas.Our previous study illustrated that LGR5 is associated with aggressiveness in NB cell lines established at different stages of treatment. Following these findings, we investigated whether LGR5 is involved in acquired drug resistance via the WNT pathway in NB cell lines.Cell lines in this study have an acquired drug resistance to vincristine (VCR) or doxorubicin (DOX).In this study, we showed LGR5-LRP6 cooperation with enhanced expression of both proteins in SHSY5YrVCR, IMR32rDOX, IMR5rVCR and IMR5rDOX NB cell lines compared to paired parental cells. We also found elevated expression of β-catenin in cell lines with acquired drug resistance is indicative of β-catenin-dependent WNT signalling.This study warrants further investigation into the role of the WNT signalling pathway in acquired drug resistance.

Investigations of dynamic amyloid-like structures of the Wnt signalling pathway by solid-state NMR

2018 ◽  
Vol 54 (32) ◽  
pp. 3959-3962 ◽  
Author(s):  
M. E. Ward ◽  
M. A. Daniëls ◽  
E. C. van Kappel ◽  
M. M. Maurice ◽  
M. Baldus
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Solid State ◽  
Magnetic Resonance ◽  
Solid State Nmr ◽  
Wnt Pathway ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Wnt Signalling Pathway ◽  
Structural Details ◽  
Nuclear Magnetic

Solid-state nuclear magnetic resonance can reveal native structural details of amyloid-like signalling proteins of the Wnt pathway.

scholarly journals Methane Saline Ameliorates Traumatic Brain Injury through Anti-Inflammatory, Antiapoptotic, and Antioxidative Effects by Activating the Wnt Signalling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Meng Li ◽  
Weiman Gao ◽  
Le Ji ◽  
Jia Li ◽  
Wanting Jiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Wnt Pathway ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Sprague Dawley ◽  
Wnt Signalling Pathway ◽  
Sprague Dawley Rats ◽  
Antioxidative Effects ◽  
Anti Inflammatory

Objective. Methane saline (MS) can be used to treat many diseases via its anti-inflammatory, antiapoptotic, and antioxidative activities. However, to date, there is no published evidence as to whether MS has any effect on traumatic brain injury (TBI). The Wnt signalling pathway regulates cell proliferation, differentiation, migration, and apoptosis; however, whether the Wnt signalling pathway regulates any effect of MS on TBI is unknown. This study was designed to explore the role of MS in the treatment of TBI and whether the Wnt pathway is involved. Methods. Sprague-Dawley rats were randomly divided into five groups: sham, TBI, TBI+10 ml/kg MS, TBI+20 ml/kg MS, and TBI+30 ml/kg MS. After induction of TBI, MS was injected intraperitoneally once daily for seven consecutive days. Neurological function was evaluated by the Neurological Severity Score (NSS) at 1, 7, and 14 days after TBI. Haematoxylin-eosin (HE) staining, inflammatory factors, neuron-specific enolase (NSE) staining, oxidative stress, and cell apoptosis were measured and compared 14 d after TBI to identify the optimal dose of MS and to investigate the effect of MS on TBI. In the second experiment, Sprague-Dawley rats were randomly divided into four groups: sham, TBI, TBI+20 ml/kg MS, and TBI+20 ml/kg MS+Dickkopf-1 (DKK-1, a specific inhibitor of the Wnt pathway). NSE, caspase-3, superoxide dismutase (SOD), Wnt3a, and β-catenin were detected by real-time PCR and Western blotting. The results from each group were compared 14 d after TBI to determine the regulatory role of the Wnt pathway. Results. Methane saline significantly inhibited inflammation, oxidative stress, and cell apoptosis, thus protecting neurons within 14 days of TBI. The best treatment effect against TBI was obtained with 20 ml/kg MS. When the Wnt pathway was inhibited, the treatment effect of MS was impaired. Conclusion. Methane saline ameliorates TBI through its anti-inflammatory, antiapoptotic, and antioxidative effects via activation of the Wnt signalling pathway, which plays a part but is not the only mechanism underlying the effects of MS. Thus, MS may be a novel strategy for treating TBI.

Molecular Docking Studies to Evaluate Small Molecule Inhibitors of Wnt/Betacatenin Signaling Pathway

2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Sankari Dantu Sai Shyama Lakshmi ◽  
Maka Sai Sailaja ◽  
Dalal Swetha ◽  
Chanda Chandrasekhar ◽  
Aluru Ranganadha Reddy
Keyword(s):  
Hydrogen Bond ◽  
Molecular Docking ◽  
Hydrogen Bonds ◽  
Wnt Pathway ◽  
Docking Studies ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Wnt Signalling Pathway ◽  
Canonical Wnt Pathway ◽  
Canonical Wnt

Canonical Wnt pathway or β catenin dependent pathway is one of the highly conserved signalling pathway which can control gene expression and regulate cell proliferation, cell adhesion, cell migration, cell polarity and organogenesis. Abnormal regulation of β catenin in the canonical wnt signalling pathway leads to transcription of several genes involved in oncogenic programs. Aberrant signalling of the canonical wnt pathway was observed in several types of cancers including hepatocarcinoma, colorectal cancer and lung cancer. Many small molecules were observed to have the potential to block the aberrant wnt signalling pathway by allosteric binding and inhibiting β catenin molecule. The current study involves screening for ligands which can have strong allosteric binds to β catenin and inhibit wnt signalling pathway. Molecular docking studies were used to evaluate the binding capacity of the selected ligands. Curcumin, Cardamonin, FH535 and ICRT-3 were used as ligands for the molecular docking study with β catenin binding Transcription factor -4 receptor. All chosen ligands have exhibited significant binding energies with the receptor. The highest -9.518272 kcal/mol with Cardamonin followed by -9.28359 kcal/mol with FH535, -8.422604 kcal/mol with curcumin and the least -8.407231 kcal/mol with ICRT-3. All the ligands showed at least 1 hydrogen bond with the target receptor whereas Cardamonin showed 3 hydrogen bonds. Curcumin is a close second forming 2 hydrogen bonds while FH535 and ICRT-3 form only 1 hydrogen bond. The 2D interactions of the ligand and the molecule are visualised by using chimera. We observed Cardamonin to have a very strong binding affinity with the target receptor. Cardamonin can be a suitable drug candidate and might have the potential to inhibit the β catenin dependent wnt signalling pathway.

scholarly journals The protein tyrosine phosphatase-BL, modulates pancreatic β-cell proliferation by interaction with the Wnt signalling pathway

2008 ◽  
Vol 197 (3) ◽  
pp. 543-552 ◽  
Author(s):  
Hannah J Welters ◽  
Alina Oknianska ◽  
Kai S Erdmann ◽  
Gerhart U Ryffel ◽  
Noel G Morgan
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Wnt Signalling Pathway

In pancreatic β-cells, increased expression of the MODY5 gene product, HNF1β, leads to enhanced rates of apoptosis and altered regulation of the cell cycle, suggesting that control of HNF1β expression may be important for the control of β-cell proliferation and viability. It is unclear how these effects of HNF1β are mediated, but previously we have identified a protein tyrosine phosphatase, (PTP)-BL, as an HNF1β-regulated protein in β-cells and have now studied the role of this protein in INS-1 β-cells. Stably transfected cells were generated, which express either wild-type (WT) or a phosphatase-deficient mutant (PTP-BL-CS) of PTP-BL conditionally under the control of a tetracycline-regulated promoter. Enhanced expression of WT PTP-BL inhibited INS-1 cell growth dose dependently, but this effect was not observed when PTP-BL-CS was expressed. Neither construct altered the rate of apoptosis. PTP-BL has been reported to interact with components of the Wnt signalling pathway, and we observed that addition of exogenous Wnt3a resulted in an increase in cell proliferation and a rise in β-catenin levels, consistent with the operation of this pathway in INS-1 cells. Up-regulation of WT PTP-BL antagonised these responses but PTP-BL-CS failed to inhibit Wnt3a-induced proliferation. The rise in β-catenin caused by Wnt3a was also suppressed by over-expression of HNF1β, suggesting that HNF1β may interact with the Wnt signalling pathway via an increase in PTP-BL levels. We conclude that PTP-BL plays an important role in the regulation of cell cycle progression in pancreatic β-cells, and that it interacts functionally with components of the Wnt signalling pathway.

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