scholarly journals Nuclear GSK-3β inhibits the canonical Wnt signalling pathway in a β-catenin phosphorylation-independent manner

Oncogene ◽  
2008 ◽  
Vol 27 (25) ◽  
pp. 3546-3555 ◽  
Author(s):  
M Caspi ◽  
A Zilberberg ◽  
H Eldar-Finkelman ◽  
R Rosin-Arbesfeld
Keyword(s):  
Wnt Signalling ◽  
Signalling Pathway ◽  
Independent Manner ◽  
Wnt Signalling Pathway ◽  
Gsk 3Β ◽  
Canonical Wnt

Glucose induces an autocrine activation of the Wnt/β-catenin pathway in macrophage cell lines

2008 ◽  
Vol 416 (2) ◽  
pp. 211-218 ◽  
Author(s):  
Sasha H. Anagnostou ◽  
Peter R. Shepherd
Keyword(s):  
Cell Lines ◽  
Nuclear Translocation ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Macrophage Cell ◽  
Glucose Levels ◽  
Wnt Signalling Pathway ◽  
Hexosamine Pathway ◽  
Number Of Genes ◽  
Canonical Wnt

The canonical Wnt signalling pathway acts by slowing the rate of ubiquitin-mediated β-catenin degradation. This results in the accumulation and subsequent nuclear translocation of β-catenin, which induces the expression of a number of genes involved in growth, differentiation and metabolism. The mechanisms regulating the Wnt signalling pathway in the physiological context is still not fully understood. In the present study we provide evidence that changes in glucose levels within the physiological range can acutely regulate the levels of β-catenin in two macrophage cell lines (J774.2 and RAW264.7 cells). In particular we find that glucose induces these effects by promoting an autocrine activation of Wnt signalling that is mediated by the hexosamine pathway and changes in N-linked glycosylation of proteins. These studies reveal that the Wnt/β-catenin system is a glucose-responsive signalling system and as such is likely to play a role in pathways involved in sensing changes in metabolic status.

scholarly journals Altered Wnt signalling in the teenage suicide brain: focus on glycogen synthase kinase-3β and β-catenin

2013 ◽  
Vol 16 (5) ◽  
pp. 945-955 ◽  
Author(s):  
Xinguo Ren ◽  
Hooriyah S. Rizavi ◽  
Mansoor A. Khan ◽  
Yogesh Dwivedi ◽  
Ghanshyam N. Pandey
Keyword(s):  
Protein Expression ◽  
Glycogen Synthase ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Glycogen Synthase Kinase ◽  
Mrna Levels ◽  
Protein Levels ◽  
Wnt Signalling Pathway ◽  
Gsk 3Β ◽  
Teenage Suicide

Abstract Glycogen synthase kinase (GSK)-3β and β-catenin are important components of the Wnt signalling pathway, which is involved in numerous physiological functions such as cognition, brain development and cell survival. Their abnormalities have been implicated in mood disorders and schizophrenia. Teenage suicide is a major public health concern; however, very little is known about its neurobiology. In order to examine if abnormalities of GSK-3β and β-catenin are associated with teenage suicide, we determined the gene and protein expression of GSK-3β and β-catenin in the prefrontal cortex (PFC) and hippocampus obtained from 24 teenage suicide victims and 24 normal control subjects. Protein expression was determined using Western blot with specific antibodies and gene expression (mRNA levels) was determined using the real-time polymerase chain reaction method. No significant change was observed in the GSK-3β protein levels either in the PFC or hippocampus of suicide victims compared to controls. However, protein levels of pGSK-3β-ser9 were significantly decreased in the PFC and hippocampus of suicide victims compared to normal controls. We also found that GSK-3β mRNA levels were significantly decreased in the PFC but not in the hippocampus of teenage suicide victims compared to controls. Mean protein and mRNA levels of β-catenin were significantly decreased in both the PFC and hippocampus of teenage suicide group compared to controls. The observation that there is a decrease in β-catenin and pGSK-3β-ser9 in the PFC and hippocampus of teenage suicide victims does indicate a disturbance in the Wnt signalling pathway in teenage suicide.

Wnt10b promotes growth of hair follicles via a canonical Wnt signalling pathway

2011 ◽  
Vol 36 (5) ◽  
pp. 534-540 ◽  
Author(s):  
Y.-H. Li ◽  
K. Zhang ◽  
J.-X. Ye ◽  
X.-H. Lian ◽  
T. Yang
Keyword(s):  
Hair Follicles ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Wnt Signalling Pathway ◽  
Canonical Wnt

scholarly journals 09-P019 The role of the non-canonical Wnt signalling pathway in branching morphogenesis

2009 ◽  
Vol 126 ◽  
pp. S156
Author(s):  
Laura L. Yates ◽  
Carsten Schnatwinkel ◽  
Jennifer N. Murdoch ◽  
Debora Bogani ◽  
Caroline J. Formstone ◽  
...  
Keyword(s):  
Branching Morphogenesis ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Wnt Signalling Pathway ◽  
Canonical Wnt

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 Cadherin 11 Inhibition Downregulates β-catenin, Deactivates the Canonical WNT Signalling Pathway and Suppresses the Cancer Stem Cell-Like Phenotype of Triple Negative Breast Cancer

2019 ◽  
Vol 8 (2) ◽  
pp. 148 ◽  
Author(s):  
Pamungkas Satriyo ◽  
Oluwaseun Bamodu ◽  
Jia-Hong Chen ◽  
Teguh Aryandono ◽  
Sofia Haryana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Integration Site ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Tumor Xenograft ◽  
Wnt Signalling Pathway ◽  
Canonical Wnt

Background: Cancer stem cells (CSCs) promote tumor progression and distant metastasis in breast cancer. Cadherin 11 (CDH11) is overexpressed in invasive breast cancer cells and implicated in distant bone metastases in several cancers. The WNT signalling pathway regulates CSC activity. Growing evidence suggest that cadherins play critical roles in WNT signalling pathway. However, CDH11 role in canonical WNT signalling and CSCs in breast cancer is poorly understood. Methods: We investigated the functional association between CDH11 and WNT signalling pathway in triple negative breast cancer (TNBC), by analyzing their expression profile in the TCGA Breast Cancer (BRCA) cohort and immunohistochemical (IHC) staining of TNBC samples. Results: We observed a significant correlation between high CDH11 expression and poor prognosis in the basal and TNBC subtypes. Also, CDH11 expression positively correlated with β-catenin, wingless type MMTV integration site (WNT)2, and transcription factor (TCF)12 expression. IHC results showed CDH11 and β-catenin expression significantly correlated in TNBC patients (p < 0.05). We also showed that siRNA-mediated loss-of-CDH11 (siCDH11) function decreases β-catenin, Met, c-Myc, and matrix metalloproteinase (MMP)7 expression level in MDA-MB-231 and Hs578t. Interestingly, immunofluorescence staining showed that siCDH11 reduced β-catenin nuclear localization and attenuated TNBC cell migration, invasion and tumorsphere-formation. Of translational relevance, siCDH11 exhibited significant anticancer efficacy in murine tumor xenograft models, as demonstrated by reduced tumor-size, inhibited tumor growth and longer survival time. Conclusions: Our findings indicate that by modulating β-catenin, CDH11 regulates the canonical WNT signalling pathway. CDH11 inhibition suppresses the CSC-like phenotypes and tumor growth of TNBC cells and represents a novel therapeutic approach in TNBC treatment.

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