Wnt signaling pathway in osteoporosis: Epigenetic regulation, interaction with other signaling pathways, and therapeutic promises

2019 ◽  
Vol 234 (9) ◽  
pp. 14641-14650 ◽  
Author(s):  
Fatemeh Amjadi‐Moheb ◽  
Haleh Akhavan‐Niaki
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Epigenetic Regulation ◽  
Wnt Signaling Pathway

scholarly journals Genetic Polymorphism in Extracellular Regulators of Wnt Signaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Garima Sharma ◽  
Ashish Ranjan Sharma ◽  
Eun-Min Seo ◽  
Ju-Suk Nam
Keyword(s):  
Genetic Polymorphism ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
The Other ◽  
Present Review ◽  
Receptor Complex ◽  
Related Proteins ◽  
Related Association

The Wnt signaling pathway is mediated by a family of secreted glycoproteins through canonical and noncanonical mechanism. The signaling pathways are regulated by various modulators, which are classified into two classes on the basis of their interaction with either Wnt or its receptors. Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex. The present review discusses the disease related association of various polymorphisms in Wnt signaling modulators. Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively.

scholarly journals Modulation of Calretinin Expression in Human Mesothelioma Cells Reveals the Implication of the FAK and Wnt Signaling Pathways in Conferring Chemoresistance towards Cisplatin

2019 ◽  
Vol 20 (21) ◽  
pp. 5391 ◽  
Author(s):  
Wörthmüller ◽  
Salicio ◽  
Oberson ◽  
Blum ◽  
Schwaller
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Expression System ◽  
Single Agent ◽  
Wnt Signaling Pathway ◽  
Tumor Formation ◽  
Mesenchymal Transition

Malignant mesothelioma (MM) is an aggressive asbestos-linked neoplasm, characterized by dysregulation of signaling pathways. Due to intrinsic or acquired chemoresistance, MM treatment options remain limited. Calretinin is a Ca2+-binding protein expressed during MM tumorigenesis that activates the FAK signaling pathway, promoting invasion and epithelial-to-mesenchymal transition. Constitutive calretinin downregulation decreases MM cells’ growth and survival, and impairs tumor formation in vivo. In order to evaluate early molecular events occurring during calretinin downregulation, we generated a tightly controlled IPTG-inducible expression system to modulate calretinin levels in vitro. Calretinin downregulation significantly reduced viability and proliferation of MM cells, attenuated FAK signaling and reduced the invasive phenotype of surviving cells. Importantly, surviving cells showed a higher resistance to cisplatin due to increased Wnt signaling. This resistance was abrogated by the Wnt signaling pathway inhibitor 3289-8625. In various MM cell lines and regardless of calretinin expression levels, blocking of FAK signaling activated the Wnt signaling pathway and vice versa. Thus, blocking both pathways had the strongest impact on MM cell proliferation and survival. Chemoresistance mechanisms in MM cells have resulted in a failure of single-agent therapies. Targeting of multiple components of key signaling pathways, including Wnt signaling, might be the future method-of-choice to treat MM.

scholarly journals Autophagy Is Required for Hepatic Differentiation of Hepatic Progenitor Cells via Wnt Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jianxing Zeng ◽  
Yingying Jing ◽  
Qionglan Wu ◽  
Jinhua Zeng ◽  
Lixin Wei ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Progenitor Cells ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Hepatic Progenitor Cells ◽  
Hepatic Differentiation ◽  
Development And Differentiation ◽  
Progenitor Cell Line

The molecular mechanisms regulating differentiation of hepatic progenitor cells (HPCs), which play pivotal roles in liver regeneration and development, remain obscure. Autophagy and Wnt signaling pathways regulate the development and differentiation of stem cells in various organs. However, the roles of autophagy and Wnt signaling pathways in hepatic differentiation of HPCs are not well understood. Here, we describe the effects of autophagy and Wnt signaling pathways during hepatic differentiation of HPCs. We used a well-established rat hepatic progenitor cell line called WB-F344, which was treated with differentiation medium to promote differentiation of WB-F344 cells along the hepatic phenotype. Firstly, autophagy was highly activated in HPCs and gradually decreased during hepatic differentiation of HPCs. Induction of autophagy by rapamycin or starvation suppressed hepatic differentiation of HPCs. Secondly, Wnt3a signaling pathway was downregulated, and Wnt5a signaling pathway was upregulated in hepatic differentiation of HPCs. At last, Wnt3a signaling pathway was enhanced, and Wnt5a signaling pathway was inhibited by activation of autophagy during hepatic differentiation of HPCs. In summary, these results demonstrate that autophagy regulates hepatic differentiation of hepatic progenitor cells through Wnt signaling pathway.

scholarly journals Epigenetic regulation of Wnt signaling pathway in urological cancer

Epigenetics ◽  
2010 ◽  
Vol 5 (4) ◽  
pp. 343-351 ◽  
Author(s):  
Vera L. Costa ◽  
Rui Henrique ◽  
Franclim R. Ribeiro ◽  
João R. Carvalho ◽  
Jorge Oliveira ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Epigenetic Regulation ◽  
Wnt Signaling Pathway ◽  
Urological Cancer

557 Epigenetic Regulation of WNT Signaling Pathway Genes in Inflammatory Bowel Disease (IBD) Neoplasia

2008 ◽  
Vol 134 (4) ◽  
pp. A-848-A-849
Author(s):  
Mashaal Dhir ◽  
Elizabeth A. Montgomery ◽  
Kornel Schuebel ◽  
Susan L. Gearhart ◽  
Nita Ahuja
Keyword(s):  
Inflammatory Bowel Disease ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Epigenetic Regulation ◽  
Bowel Disease ◽  
Wnt Signaling Pathway ◽  
Inflammatory Bowel

scholarly journals Activation of the Hedgehog and Wnt/β-Catenin Signaling Pathways in Basal Cell Carcinoma

2021 ◽  
pp. 506-512
Author(s):  
Tomoaki Takada
Keyword(s):  
Basal Cell Carcinoma ◽  
Wnt Signaling ◽  
Cell Carcinoma ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Basal Cell ◽  
Transcriptional Activation ◽  
Wnt Signaling Pathway ◽  
Downstream Effectors ◽  
Mrna Binding

In basal cell carcinoma (BCC) tumorigenesis, interaction between Hedgehog (Hh) and Wnt/β-catenin (Wnt) signaling pathways has been investigated, but not completely elucidated. Here, a case of sporadic BCC in an 80-year-old man is presented, and the effectiveness of SMO inhibitors in case of relapse is predicted. The aim of this study was to determine whether the SMO inhibitors can be effective in treating this individual should the tumor recur in the future. Immunohistochemistry (IHC) was performed in a tumor and the adjacent skin tissue from the patient. IHC within the same BCC tissue specimen revealed that Glioma-associated oncogene 1 (GLI1) and Smoothened (SMO) in the Hh signaling pathway and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in the Wnt signaling pathway were overexpressed. Hh and Wnt signaling pathways were activated. These findings suggest that the patient might be resistant to treatment with SMO inhibitors because of the interaction between Hh and Wnt signaling pathways. Overexpression of GLI1 leads to transcriptional activation, making it an attractive molecular target for anticancer therapy owing to the downstream effectors of the cascade.

scholarly journals Novel newt regeneration genes regulate Wingless signaling to restore patterning in Drosophila eye

2021 ◽  
Author(s):  
Abijeet Singh Mehta ◽  
Prajakta Deshpande ◽  
Anuradha Venkatakrishnan Chimata ◽  
Panagiotis A. Tsonis ◽  
Amit Singh
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Ectopic Expression ◽  
Wnt Signaling Pathway ◽  
Protein S ◽  
Photoreceptor Cells ◽  
Body Parts ◽  
Regeneration Potential ◽  
Regeneration Capability

AbstractA fundamental process of regeneration, which varies among animals, recruits conserved signaling pathways to restore missing parts. Only a few animals like newts can repeatedly regenerate lost body parts throughout their lifespan that can be attributed to strategic regulation of conserved signaling pathways by newt’s regeneration tool-kit genes. Here we report the use of a genetically tractable Drosophila eye model to demonstrate the regeneration potential of a group of unique protein(s) from newt (Notophthalmus viridescens), which when ectopically expressed can significantly rescue missing photoreceptor cells in a Drosophila eye mutant. These newt proteins with signal peptides motifs exhibit non-cell-autonomous rescue properties and their regeneration potential even extends into later stages of fly development. Ectopic expression of these newt genes can rescue eye mutant phenotype by promoting cell proliferation and blocking cell death. These novel newt genes downregulate the evolutionarily conserved Wingless (Wg)/Wnt signaling pathway to promote rescue. Modulation of Wg/Wnt signaling levels by using antagonists or agonists of Wg/Wnt signaling pathway in eye mutant background where newt gene(s) is ectopically expressed suggests that Wg signaling acts downstream of newt genes. Our data highlights the regeneration potential of novel newt proteins that regulate conserved pathways to trigger a robust regeneration response in Drosophila model with weak regeneration capability.

scholarly journals Epigenetic Regulation of WNT Signaling Pathway Genes in Inflammatory Bowel Disease (IBD) Associated Neoplasia

2008 ◽  
Vol 12 (10) ◽  
pp. 1745-1753 ◽  
Author(s):  
Mashaal Dhir ◽  
Elizabeth A. Montgomery ◽  
Sabine C. Glöckner ◽  
Kornel E. Schuebel ◽  
Craig M. Hooker ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Epigenetic Regulation ◽  
Bowel Disease ◽  
Wnt Signaling Pathway ◽  
Inflammatory Bowel

scholarly journals The Crosstalk between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication

2020 ◽  
Vol 21 (23) ◽  
pp. 9107
Author(s):  
Janine Wörthmüller ◽  
Curzio Rüegg
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Functional Interaction ◽  
Mucosal Regeneration ◽  
Pancreatic Cancers ◽  
Dependent Relationship ◽  
Context Specific ◽  
Wnt Inhibitors

Focal adhesion kinase (FAK) and Wnt signaling pathways are important contributors to tumorigenesis in several cancers. While most results come from studies investigating these pathways individually, there is increasing evidence of a functional crosstalk between both signaling pathways during development and tumor progression. A number of FAK–Wnt interactions are described, suggesting an intricate, context-specific, and cell type-dependent relationship. During development for instance, FAK acts mainly upstream of Wnt signaling; and although in intestinal homeostasis and mucosal regeneration Wnt seems to function upstream of FAK signaling, FAK activates the Wnt/β-catenin signaling pathway during APC-driven intestinal tumorigenesis. In breast, lung, and pancreatic cancers, FAK is reported to modulate the Wnt signaling pathway, while in prostate cancer, FAK is downstream of Wnt. In malignant mesothelioma, FAK and Wnt show an antagonistic relationship: Inhibiting FAK signaling activates the Wnt pathway and vice versa. As the identification of effective Wnt inhibitors to translate in the clinical setting remains an outstanding challenge, further understanding of the functional interaction between Wnt and FAK could reveal new therapeutic opportunities and approaches greatly needed in clinical oncology. In this review, we summarize some of the most relevant interactions between FAK and Wnt in different cancers, address the current landscape of Wnt- and FAK-targeted therapies in different clinical trials, and discuss the rationale for targeting the FAK–Wnt crosstalk, along with the possible translational implications.

Sign in / Sign up

Export Citation Format

Share Document