Dissecting the impact of Frizzled receptors in Wnt/β-catenin signaling of human mesenchymal stem cells
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Thomas Kolben
Abstract
Wnt/β-catenin signaling is of fundamental importance in the regulation of self-renewal, migration/invasion, and differentiation of human mesenchymal stem cells (hMSCs). Because little information is available about the function of Frizzled receptors (Fzds) as the main receptors of Wnt proteins in hMSCs, we first performed comparative Fzd mRNA expression profiling. Fzd9 and Fzd10 were not expressed in hMSCs. While Fzd3 was expressed at low levels in hMSCs, the other Fzds exhibited high expression rates. Activation and repression of Wnt signaling in hMSCs revealed that the expression levels of Fzd1, Fzd6, and Fzd7 are positively correlated with the Wnt/β-catenin activation status, whereas Fzd8 exhibited an inverse relation. For studying the functional relevance of Fzds in Wnt/β-catenin signaling, RNA interference, ectopic expression studies, and rescue approaches were performed in hMSCs carrying a highly sensitive TCF/LEF reporter gene system (Gaussia luciferase). We found that, Fzd1, Fzd5, Fzd7, and Fzd8 are largely involved in Wnt/β-catenin signaling of hMSCs. Moreover, the knockdown of Fzd5 can be compensated by the ectopic expression of Fzd7. Conversely, the ectopic expression of Fzd5 in Fzd7-knockdown hMSCs resulted in a rescue of Wnt/β-catenin signaling, pointing to a functional redundancy of Fzd5 and Fzd7.
©2012 by Walter de Gruyter Berlin Boston
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Articles in the same Issue
- Masthead
- Masthead
- Guest Editorial
- Highlight: 29th Winter School on Proteinases and Their Inhibitors
- Highlight: 29th Winter School on Proteinases and their Inhibitors
- Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases
- Effects of cathepsin K deficiency on intercellular junction proteins, luminal mucus layers, and extracellular matrix constituents in the mouse colon
- Three-dimensional cultures modeling premalignant progression of human breast epithelial cells: role of cysteine cathepsins
- Cysteine cathepsins are not critical for TRAIL- and CD95-induced apoptosis in several human cancer cell lines
- Dissecting the impact of Frizzled receptors in Wnt/β-catenin signaling of human mesenchymal stem cells
- Overexpression of the urokinase receptor splice variant uPAR-del4/5 in breast cancer cells affects cell adhesion and invasion in a dose-dependent manner and modulates transcription of tumor-associated genes
- IGF-I receptor phosphorylation is impaired in cathepsin X-deficient prostate cancer cells
- Cell surface engineering of renal cell carcinoma with glycosylphosphatidylinositol-anchored TIMP-1 blocks TGF-β1 activation and reduces regulatory ID gene expression
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- Review
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- Proteolysis
- Characterization of angiotensin I-converting enzyme N-domain selectivity using positional-scanning combinatorial libraries of fluorescence resonance energy transfer peptides
- Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis
