Wnt Glycation Inhibits Canonical Signaling

Ye, Zhen-Nan; Mittag, Sonnhild; Schmidt, Martin; Simm, Andreas; Horstkorte, Rüdiger; Huber, Otmar

doi:10.3390/cells8111320

Cited by 7 publications

(5 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4A-4F). Consistent with the increased nuclear translocation of CTNNB1, Wnt16 OE further increased the TCF/LEF reporter activity in a Topflash assay (p < 0.05), which indicates Wnt/β-catenin signaling pathway activation (Ye et al, 2019). But Wnt16 OE along with Wnt3a, a canonical Wnt that is thought to activate Wnt/β-catenin signaling pathway, showed almost similar effect when Wnt16 OE or Wnt3a existed alone; meanwhile DKK-1, a specific inhibitor of the target of the Wnt/β-catenin pathway, restrained Wnt16's effect (Fig.…”

Section: Wnt16 Activating Canonical β-Catenin Pathwaysupporting

confidence: 52%

Wnt16 signaling promotes osteoblast differentiation of periosteal derived cells in vitro and in vivo

Jin

Sun

Fang

et al. 2020

PeerJ

View full text Add to dashboard Cite

Background Periosteum plays critical roles in de novo bone formation and fracture repair. Wnt16 has been regarded as a key regulator in periosteum bone formation. However, the role of Wnt16 in periosteum derived cells (PDCs) osteogenic differentiation remains unclear. The study goal is to uncover whether and how Wnt16 acts on the osteogenesis of PDCs. Methods We detected the variation of Wnt16 mRNA expression in PDCs, which were isolated from mouse femur and identified by flow cytometry, cultured in osteogenic medium for 14 days, then knocked down and over-expressed Wnt16 in PDCs to analysis its effects in osteogenesis. Further, we seeded PDCs (Wnt16 over-expressed/vector) in β-tricalcium phosphate cubes, and transplanted this complex into a critical size calvarial defect. Lastly, we used immunofluorescence, Topflash and NFAT luciferase reporter assay to study the possible downstream signaling pathway of Wnt16. Results Wnt16 mRNA expression showed an increasing trend in PDCs under osteogenic induction for 14 days. Wnt16 shRNA reduced mRNA expression of Runx2, collage type I (Col-1) and osteocalcin (OCN) after 7 days of osteogenic induction, as well as alizarin red staining intensity after 21days. Wnt16 also increased the mRNA expression of Runx2 and OCN and the protein production of Runx2 and Col-1 after 2 days of osteogenic stimulation. In the orthotopic transplantation assay, more bone volume, trabecula number and less trabecula space were found in Wnt16 over-expressed group. Besides, in the newly formed tissue Brdu positive area was smaller and Col-1 was larger in Wnt16 over-expressed group compared to the control group. Finally, Wnt16 upregulated CTNNB1/β-catenin expression and its nuclear translocation in PDCs, also increased Topflash reporter luciferase activity. By contrast, Wnt16 failed to increase NFAT reporter luciferase activity. Conclusion Together, Wnt16 plays a positive role in regulating PDCs osteogenesis, and Wnt16 may have a potential use in improving bone regeneration.

show abstract

Section: Wnt16 Activating Canonical β-Catenin Pathwaysupporting

confidence: 52%

Wnt16 signaling promotes osteoblast differentiation of periosteal derived cells in vitro and in vivo

Jin

Sun

Fang

et al. 2020

PeerJ

View full text Add to dashboard Cite

show abstract

“…Furthermore, L-M(TK-) cells (parental and WNT3a expressing) were cultured in DMEM containing 10% (v/v) FBS, 40 µg/mL gentamicin, and 100 µg/mL G418, before being used for production of conditioned media. The production of high titers of WNT3a protein by these cells was verified previously [55].…”

Section: Cells and Cell Culturesupporting

confidence: 63%

WNT3a Signaling Inhibits Aromatase Expression in Breast Adipose Fibroblasts—A Possible Mechanism Supporting the Loss of Estrogen Responsiveness of Triple-Negative Breast Cancers

Kaiser

Eiselt

Bechler

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Estrogen-dependent breast cancers rely on a constant supply of estrogens and expression of estrogen receptors. Local biosynthesis, by aromatase in breast adipose fibroblasts (BAFs), is their most important source for estrogens. Triple-negative breast cancers (TNBC) rely on other growth-promoting signals, including those from the Wnt pathway. In this study, we explored the hypothesis that Wnt signaling alters the proliferation of BAFs, and is involved in regulation of aromatase expression in BAFs. Conditioned medium (CM) from TNBC cells and WNT3a consistently increased BAF growth, and reduced aromatase activity up to 90%, by suppression of the aromatase promoter I.3/II region. Database searches identified three putative Wnt-responsive elements (WREs) in the aromatase promoter I.3/II. In luciferase reporter gene assays, promoter I.3/II activity was inhibited by overexpression of full-length T-cell factor (TCF)-4 in 3T3-L1 preadipocytes, which served as a model for BAFs. Full-length lymphoid enhancer-binding factor (LEF)-1 increased the transcriptional activity. However, TCF-4 binding to WRE1 in the aromatase promoter, was lost after WNT3a stimulation in immunoprecipitation-based in vitro DNA-binding assays, and in chromatin immunoprecipitation (ChIP). In vitro DNA-binding assays, ChIP, and Western blotting revealed a WNT3a-dependent switch of nuclear LEF-1 isoforms towards a truncated variant, whereas β-catenin levels remained unchanged. This LEF-1 variant revealed dominant negative properties, and most likely recruited enzymes involved in heterochromatin formation. In addition, WNT3a induced the replacement of TCF-4 by the truncated LEF-1 variant, on WRE1 of the aromatase promoter I.3/II. The mechanism described here may be responsible for the loss of aromatase expression predominantly associated with TNBC. Tumors with (strong) expression of Wnt ligands actively suppress aromatase expression in BAFs. Consequently a reduced estrogen supply could favor the growth of estrogen-independent tumor cells, which consequently would make estrogen receptors dispensable. In summary, canonical Wnt signaling within (cancerous) breast tissue may be a major factor controlling local estrogen synthesis and action.

show abstract

“…STF293 cells were kept under selective conditions with 0.1 mg/mL G418 (PAN-Biotech, Aidenbach, Germany). Wnt3a-conditioned medium and control medium were produced by Wnt3a-transfected and empty vector-transfected L-M-(TK-) cells, respectively, as described in [ 55 ].…”

Section: Methodsmentioning

confidence: 99%

Hyperforin and Myrtucommulone Derivatives Act as Natural Modulators of Wnt/β-Catenin Signaling in HCT116 Colon Cancer Cells

Knauthe

Mittag

Bloch

et al. 2022

IJMS

View full text Add to dashboard Cite

The therapeutic activities of natural plant extracts have been well known for centuries. Many of them, in addition to antiviral and antibiotic effects, turned out to have anti-tumor activities by targeting different signaling pathways. The canonical Wnt pathway represents a major tumorigenic pathway deregulated in numerous tumor entities, including colon cancer. Here, we investigated the acylphloroglucinols hyperforin (HF) from St. John’s wort (Hypericum perforatum L.) and myrtucommulone A (MC A) from myrtle (Myrtus communis) and semi-synthetic derivatives thereof (HM 177, HM 297, HM298) for their effects on Wnt/β-catenin signaling. None of these substances revealed major cytotoxicity on STF293 embryonic kidney and HCT116 colon carcinoma cells at concentrations up to 10 μM. At this concentration, HF and HM 177 showed the strongest effect on cell proliferation, whereas MC A and HM 177 most prominently inhibited anchorage-independent growth of HCT116 cells. Western blot analyses of active β-catenin and β-catenin/TCF reporter gene assays in STF293 cells revealed inhibitory activities of HF, MC A and HM 177. In line with this, the expression of endogenous Wnt target genes, Axin and Sp5, in HCT116 cells was significantly reduced. Our data suggest that the acylphloroglucinols hyperforin, myrtucommulone A and its derivative HM 177 represent potential new therapeutic agents to inhibit Wnt/β-catenin signaling in colon cancer.

show abstract

Wnt Glycation Inhibits Canonical Signaling

Cited by 7 publications

References 58 publications

Wnt16 signaling promotes osteoblast differentiation of periosteal derived cells in vitro and in vivo

Wnt16 signaling promotes osteoblast differentiation of periosteal derived cells in vitro and in vivo

WNT3a Signaling Inhibits Aromatase Expression in Breast Adipose Fibroblasts—A Possible Mechanism Supporting the Loss of Estrogen Responsiveness of Triple-Negative Breast Cancers

Hyperforin and Myrtucommulone Derivatives Act as Natural Modulators of Wnt/β-Catenin Signaling in HCT116 Colon Cancer Cells

Contact Info

Product

Resources

About