Experimental modulation of the canonical Wnt-signalling pathway in primary cell cultures of craniopharyngiomas

2008 ◽  
Vol 116 (09) ◽  
Author(s):  
A Hölsken ◽  
J Kreutzer ◽  
M Buchfelder ◽  
R Fahlbusch ◽  
I Blümcke ◽  
...  
2008 ◽  
Vol 416 (2) ◽  
pp. 211-218 ◽  
Author(s):  
Sasha H. Anagnostou ◽  
Peter R. Shepherd

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.


2011 ◽  
Vol 36 (5) ◽  
pp. 534-540 ◽  
Author(s):  
Y.-H. Li ◽  
K. Zhang ◽  
J.-X. Ye ◽  
X.-H. Lian ◽  
T. Yang

2009 ◽  
Vol 126 ◽  
pp. S156
Author(s):  
Laura L. Yates ◽  
Carsten Schnatwinkel ◽  
Jennifer N. Murdoch ◽  
Debora Bogani ◽  
Caroline J. Formstone ◽  
...  

Author(s):  
Sankari Dantu Sai Shyama Lakshmi ◽  
Maka Sai Sailaja ◽  
Dalal Swetha ◽  
Chanda Chandrasekhar ◽  
Aluru Ranganadha Reddy

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.


2019 ◽  
Vol 8 (2) ◽  
pp. 148 ◽  
Author(s):  
Pamungkas Satriyo ◽  
Oluwaseun Bamodu ◽  
Jia-Hong Chen ◽  
Teguh Aryandono ◽  
Sofia Haryana ◽  
...  

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.


2020 ◽  
Vol 32 (5) ◽  
pp. 522
Author(s):  
Xue Wang ◽  
Ziming Wang ◽  
S. O. Adeniran ◽  
Fushuo Huang ◽  
Mingjun Ma ◽  
...  

The gap junction protein connexin (Cx) 43 between adjacent Sertoli cells (SCs) is the main testicular factor regulating the growth and development of SCs, and plays a vital role in controlling cell differentiation and maturation. However, the endogenous testicular factors that regulate Cx43 and the downstream signalling pathways that mediate Cx43-dependent SC differentiation are unclear. In this study, high-purity SCs were isolated from newborn calves’ testes by differential adherence. The SCs were then cultured invitro and treated with short interference RNA to knockdown endogenous Wilms’ tumour 1 (WT1). In WT1-knockdown SCs, Cx43 expression was upregulated. To elucidate the intracellular signalling mechanism of Cx43 in the differentiation and maturation of immature SCs, SCs were treated simultaneously with non-canonical Wnt signalling inhibitors CCG-1423 and GO-6983; in these SCs, Cx43 expression was upregulated. Together, these data indicate that WT1 negatively regulates the expression of Cx43 produced from SCs via a non-canonical Wnt signalling pathway in cultured bovine SCs.


Oncogene ◽  
2008 ◽  
Vol 27 (25) ◽  
pp. 3546-3555 ◽  
Author(s):  
M Caspi ◽  
A Zilberberg ◽  
H Eldar-Finkelman ◽  
R Rosin-Arbesfeld

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