scholarly journals Canonical Wnt signaling Is Involved in Anterior Regeneration of the Annelid Aeolosoma viride

2020 ◽  
Author(s):  
Cheng-Yi Chen ◽  
Wei-Ting Yueh ◽  
Jiun-Hong Chen
Keyword(s):  
Wnt Signaling ◽  
Wnt Pathway ◽  
Wound Closure ◽  
Tissue Level ◽  
Canonical Wnt Signaling ◽  
Blastemal Cell ◽  
Underlying Mechanisms ◽  
Canonical Wnt ◽  
Anterior Regeneration

AbstractAnnelids are regenerative animals, but the underlying mechanisms await to be discovered. Because Wnt pathway is involved in animal regeneration to varying extents, we used Aeolosoma viride to interrogate whether and how this pathway plays a role in annelid anterior regeneration. We found that the expression of wnt4, β-catenin and nuclear-localized β-catenin protein were up-regulated during blastemal formation and down-regulated as anterior structures gradually reformed. Consistent with potential Wnt activities in the blastema, treatments with either Wnt pathway activator (azakenpaullone) or inhibitor (XAV939) inhibited head regeneration, which further supports a role of Wnt pathway during anterior regeneration. Detailed tissue-level examines demonstrated that wound closure and blastemal cell proliferation were impaired by over-activating the pathway, and that neuronal and musculature differentiation were affected under Wnt inhibition. Combined, gene expression and chemical inhibitor data suggest the presence of dynamic Wnt activities at different anterior regeneration stages: an initial low activity may be required for wound closure, and the following activation may signal blastemal formation and cell differentiation. In a nutshell, we propose that the canonical Wnt signaling regulates blastemal cellular responses during annelid regeneration.

scholarly journals The Role of Canonical Wnt Signaling in Regulating Radioresistance

2018 ◽  
Vol 48 (2) ◽  
pp. 419-432 ◽  
Author(s):  
Yuanyuan Zhao ◽  
Leilei Tao ◽  
Jun Yi ◽  
Haizhu Song ◽  
Longbang Chen
Keyword(s):  
Wnt Signaling ◽  
Cancer Progression ◽  
Wnt Signaling Pathway ◽  
Growth Factor Receptor ◽  
Cancer Resistance ◽  
Canonical Wnt Signaling ◽  
Damage Repair ◽  
Epidermal Growth ◽  
Canonical Wnt

Radioresistance is a major obstacle in radiotherapy for cancer, and strategies are needed to overcome this problem. Currently, radiotherapy combined with targeted therapy such as inhibitors of phosphoinosotide 3-kinase/Akt and epidermal growth factor receptor signaling have become the focus of studies on radiosensitization. Apart from these two signaling pathways, which promote radioresistance, deregulation of Wnt signaling is also associated with the radioresistance of multiple cancers. Wnts, as important messengers in the tumor microenvironment, are involved in cancer progression mainly via canonical Wnt signaling. Their role in promoting DNA damage repair and inhibiting apoptosis facilitates cancer resistance to radiation. Thus, it seems reasonable to target Wnt signaling as a method for overcoming radioresistance. Many small-molecule inhibitors that target the Wnt signaling pathway have been identified and shown to promote radiosensitization. Therefore, a Wnt signaling inhibitor may help to overcome radioresistance in cancer therapy.

The role of magnesium ions in bone regeneration involves the canonical Wnt signaling pathway

2019 ◽  
Vol 98 ◽  
pp. 246-255 ◽  
Author(s):  
Chu-Chih Hung ◽  
Amy Chaya ◽  
Kai Liu ◽  
Konstantinos Verdelis ◽  
Charles Sfeir
Keyword(s):  
Wnt Signaling ◽  
Bone Regeneration ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Magnesium Ions ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

Expression of Wnt-3a in Myeloma Cells Inhibits the Osteolytic Phenotype In-Vivo.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3420-3420
Author(s):  
Ya-Wei Qiang ◽  
Shmuel Yaccoby ◽  
John D. Shaughnessy
Keyword(s):  
Bone Resorption ◽  
Wnt Signaling ◽  
Myeloma Cell ◽  
Beta Catenin ◽  
Canonical Wnt Signaling ◽  
Myeloma Cell Line ◽  
Myeloma Cells ◽  
Canonical Wnt

Wnt signaling is a highly conserved signal transduction pathway involved in embryonic development. Inappropriate canonical Wnt signaling resulting in beta-catenin stabilization, is associated with several types of human cancers. Multiple myeloma plasma cells express Wnt receptors, Wnt ligands and soluble Wnt inhibitors. Wnt signaling is central to osteoblast and osteoclasts development and secretion of Wnt signaling inhibitors by myeloma cells is thought to contribute to the osteolytic phenotype seen in this disease and prostate cancer. While it is now clear that MM cells can signal through both canonical and non-canonical mechanisms, there are conflicting data as to the direct role of Wnt signaling in myeloma cell biology. Others have shown that Wnts cause proliferation of myeloma cells; while we have shown that canonical Wnts cause morphological changes and migration, but not cell proliferation. To further elucidate the role of canonical Wnt signaling in myeloma and myeloma bone disease we used limiting dilutions in the presence of G418 to create two independent stable clones of the myeloma cell line NCI-H929 expressing Wnt-3A (H929/W3A), which is not expressed in myeloma, and an empty vector (H929/EV). Because Wnt antibodies are not available we cloned Wnt-3A as a fusion protein with hemagglutinin (HA). Western blots against HA revealed a positive band of the expected size only in the H929/W3A clones. GST-E-cadherin binding assay and Western blot analysis revealed elevated levels of total and free beta-catenin in H929/W3A relative to H929/EV, however, there this was not associated with increased growth or proliferation by MTT assay. To determine the in-vivo growth characteristics and effects on bone resorption of Wnt-3A producing cells, we transplanted the lines into a human bone implanted the flank of SCID mice. Tumor growth rate as determined by increased production of human immunoglobulin in mice serum was significantly slower in the Wnt-3A transfected cells relative to controls (P < .05). Loss of bone mineral density (BMD) of the implanted bones engrafted with H929/W3A cells was lower than in bones engrafted with H929/EV cells (P < .05). Reduced tumor burden and BMD loss was also visualized on x-ray radiographs. Taken together these data indicate that all factors promoting bone resorption produced by or elicited by the myeloma cell line H929 are subordinate to canonical Wnt signaling and that prevention of bone destruction may help control myeloma progression.

AML Survival and In Vivo Progression Is Dependent On β-Catenin Signaling.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2398-2398
Author(s):  
Elena K Siapati ◽  
Magda Papadaki ◽  
Zoi Kozaou ◽  
Erasmia Rouka ◽  
Evridiki Michali ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Wnt Signaling Pathway ◽  
Canonical Wnt Signaling ◽  
Down Regulation ◽  
Canonical Wnt

Abstract Abstract 2398 Poster Board II-375 B-catenin is the central effector molecule of the canonical wnt signaling pathway which governs cell fate and differentiation during embryogenesis as well as self-renewal of hematopoietic stem cells. Deregulation of the pathway has been observed in various malignancies including myeloid leukemias where over-expression of β-catenin is an independent adverse prognostic factor. In the present study we examined the functional outcome of stable β-catenin down-regulation through lentivirus-mediated expression of short hairpin RNA (shRNA). Reduction of the β-catenin levels in AML cell lines and patient samples diminished their in vitro proliferation ability without significantly affecting cell viability. In order to study the role of β-catenin in vivo, we transplanted leukemic cell lines with control or reduced levels of β-catenin in NOD/SCID animals and analyzed the engraftment levels in the bone marrow. We observed that while the immediate homing of the cells was not affected by the β-catenin levels, the bone marrow engraftment was directly dependent on its levels. Subsequent examination of bone marrow sections revealed that the reduced engraftment was partly due to the inability of the cells with lower β-catenin levels to dock to the endosteal niches, a finding that was confirmed in competitive repopulation assays with untransduced cells. When we examined the expression levels of adhesion molecules and integrins in engrafted cells in vivo, we observed a significant down-regulation of CD44 expression, a molecule that participates in the interaction of HSCs with the niche. Gene expression analysis of the components of the wnt signaling pathway showed that the pathway is subject to tight transcriptional regulation with minor expression deviations. We did, however, observe an up-regulation in components that participate in the non-canonical wnt signaling pathways such as the WNT5B ligand. Ongoing experiments in normal cord blood CD34+ cells will determine the in vivo role of β-catenin signaling in normal hematopoietic progenitors. In conclusion, our study showed that β-catenin comprises an integral part in the development and progression of AML in vivo, indicating that manipulation of the wnt pathway may hold a therapeutic potential in the management of AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Role of non-canonical Wnt signaling in osteoblast maturation on microstructured titanium surfaces

2011 ◽  
Vol 7 (6) ◽  
pp. 2740-2750 ◽  
Author(s):  
Rene Olivares-Navarrete ◽  
Sharon L. Hyzy ◽  
Daphne L. Hutton ◽  
Ginger R. Dunn ◽  
Christoph Appert ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Canonical Wnt Signaling ◽  
Titanium Surfaces ◽  
Canonical Wnt ◽  
Osteoblast Maturation

scholarly journals Role of canonical Wnt signaling in endometrial carcinogenesis

2012 ◽  
Vol 12 (1) ◽  
pp. 51-62 ◽  
Author(s):  
Thanh H Dellinger ◽  
Kestutis Planutis ◽  
Krishnansu S Tewari ◽  
Randall F Holcombe
Keyword(s):  
Wnt Signaling ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

scholarly journals MULTIFACTORIAL PATHOGENESIS OF OSTEOPOROSIS AND THE ROLE OF GENES OF CANONICAL WNT-SIGNALING PATHWAY

2015 ◽  
Vol 18 (2) ◽  
pp. 15-19
Author(s):  
E A Mailyan
Keyword(s):  
Genetic Analysis ◽  
Wnt Signaling ◽  
Candidate Genes ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Scientific Research ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt ◽  
Skeleton Formation

Nowadays, multifactorial nature of osteoporosis does not raise any doubts. Besides, it should be noted that about 90% disease cases are determined genetically. In 1990-s a number of candidate genes mutations were established which increase the risk of osteoporosis development. VDR, ESR1, ESR2, COLIA1, PTH, CT, CTR, BGP, AR, GCCR, TGFB1, IL-6, IGF1, IL-1ra, OPG were considered to be this kind of genes. New genetic analysis technologies (GWAS, etc.) gave the opportunity to expand our conception about multi genomic pathogenesis of osteoporosis and to point out a new group of genes candidate - a canonical Wnt-signaling pathway genes (CTNNB1, SOST, FOXC2, FOXL1, LRP4, LRP5, WNT1, WNT3, WNT16, DKK1, AXIN1, JAG1, etc.). Extreme importance of canonical Wnt-signaling pathway and genes given above in skeleton formation and its strength necessitate the need for further scientific research and opens perspective to improve osteoporosis diagnostics, treatment and prognosis.

scholarly journals A CRISPR knockout screen reveals new regulators of canonical Wnt signaling

Oncogenesis ◽  
2021 ◽  
Vol 10 (9) ◽  
Author(s):  
Tamar Evron ◽  
Michal Caspi ◽  
Michal Kazelnik ◽  
Yarden Shor-Nareznoy ◽  
Shir Armoza-Eilat ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Wnt Pathway ◽  
Signal Transduction Pathway ◽  
Rapid Identification ◽  
Initiation Factor ◽  
Canonical Wnt Signaling ◽  
New Genes ◽  
A Genome ◽  
Signaling Activation ◽  
Canonical Wnt

AbstractThe Wnt signaling pathways play fundamental roles during both development and adult homeostasis. Aberrant activation of the canonical Wnt signal transduction pathway is involved in many diseases including cancer, and is especially implicated in the development and progression of colorectal cancer. Although extensively studied, new genes, mechanisms and regulatory modulators involved in Wnt signaling activation or silencing are still being discovered. Here we applied a genome-scale CRISPR-Cas9 knockout (KO) screen based on Wnt signaling induced cell survival to reveal new inhibitors of the oncogenic, canonical Wnt pathway. We have identified several potential Wnt signaling inhibitors and have characterized the effects of the initiation factor DExH-box protein 29 (DHX29) on the Wnt cascade. We show that KO of DHX29 activates the Wnt pathway leading to upregulation of the Wnt target gene cyclin-D1, while overexpression of DHX29 inhibits the pathway. Together, our data indicate that DHX29 may function as a new canonical Wnt signaling tumor suppressor and demonstrates that this screening approach can be used as a strategy for rapid identification of novel Wnt signaling modulators.

Normal hematopoiesis and hematologic malignancies: Role of canonical Wnt signaling pathway and stromal microenvironment

2013 ◽  
Vol 1835 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Paul Faustin Seke Etet ◽  
Lorella Vecchio ◽  
Patrice Bogne Kamga ◽  
Elias Nchiwan Nukenine ◽  
Mauro Krampera ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Hematologic Malignancies ◽  
Canonical Wnt Signaling ◽  
Stromal Microenvironment ◽  
Canonical Wnt
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