Physiological inhibitors of Wnt signaling

Filipovich, Alexandra H.; Gehrke, Iris; Poll-Wolbeck, Simon Jonas; Kreuzer, Karl‐Anton

doi:10.1111/j.1600-0609.2011.01592.x

Cited by 28 publications

(25 citation statements)

References 144 publications

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“…The Dsh expression also needs to be activated, thereby causing downstream JHK or RhoA activation. The Wnt/Ca 2+ pathway can increase intracellular calcium levels via G proteins [24]. Although Wnt4 is also able to activate the non-canonical Wnt signaling pathway, in this experiment, we believe that the regulatory role of AS-IV for Wnt4 still contributes to the inhibition of Wnt/β-catenin signaling pathway.…”

Section: Discussionmentioning

confidence: 76%

Astragaloside IV Inhibits the Up-Regulation of Wnt/β-Catenin Signaling in Rats with Unilateral Ureteral Obstruction

Wang¹,

Chi²,

Yuan³

et al. 2014

Cell Physiol Biochem

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Objective: To investigate the effect of Astragaloside IV (AS-IV) on the regulation of the Wnt/β-catenin signaling pathway in rats with unilateral ureteral obstruction (UUO). Methods: Rat renal interstitial fibrosis models were prepared using unilateral ureteral ligation. Rats were randomly divided into sham group, sham group with AS-IV (33mg/kg), unilateral ureteral obstruction group, and unilateral ureteral obstruction group receiving varied doses of AS-IV (3.3, 10, and 33 mg/kg). Immunohistochemical analysis, real-time fluorescence quantitative PCR (FQ-PCR), and western blot were used to detect the expression of genes and proteins associated with the Wnt/β-catenin signaling pathway in renal tissues. Results: Levels of Wnt3, Wnt4, and Frizzled gene expression increased significantly in the UUO model; AS-IV was associated with the downregulation of the expression of Wnt3, Wnt4, Frizzled4, p-LRP5, p-LRP6, disheveled, β-catenin, LEF-1, TCF-1, Snail, Jagged 1, Twist, MMP2, and MMP7 proteins in a concentration-dependent manner, while the expression of APC, CK1, and E-cadherin was increased. Conclusions: AS-IV effectively inhibits the up-regulation of proteins in the Wnt/β-catenin signaling pathway in UUO-model rats, indicating its possible inhibitory effects on renal interstitial fibrosis.

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Section: Discussionmentioning

confidence: 76%

Astragaloside IV Inhibits the Up-Regulation of Wnt/β-Catenin Signaling in Rats with Unilateral Ureteral Obstruction

Wang¹,

Chi²,

Yuan³

et al. 2014

Cell Physiol Biochem

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“…In addition to the intracellular negative regulators of Wnt/β-catenin signaling (e.g. GSK3β, APC, and Axin2), the extracellular negative regulators consists of Cerberus, the Dickkopf (Dkk) protein family, Schlerostin/SOST, secreted frizzled-related proteins (sFRPs) and Wnt inhibitory factor-1 (WIF-1) [4, 5]. Mutations in Wnt/β-catenin signaling components, aberrant epigenetic regulation of Wnt signaling antagonists and up-regulation of Wnt proteins and their receptors contribute to the development of a variety of diseases including cancer [4-6].…”

Section: The Canonical and The Non-canonical Wnt Signaling Pathwaysmentioning

confidence: 99%

Frizzled7 as an emerging target for cancer therapy

King

Zhang

Suto

et al. 2012

Cellular Signalling

109

112

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Wnt proteins are secreted glycoproteins that bind to the N-terminal extra-cellular cysteine-rich domain of the Frizzled (Fzd) receptor family. The Fzd receptors can respond to Wnt proteins in the presence of Wnt co-receptors to activate the canonical and non-canonical Wnt pathways. Recent studies indicated that, among the Fzd family, Fzd7 is the Wnt receptor most commonly upregulated in a variety of cancers including colorectal cancer, hepatocellular carcinoma and triple negative breast cancer. Fzd7 plays an important role in stem cell biology and cancer development and progression. In addition, it has been demonstrated that siRNA knockdown of Fzd7, the anti-Fzd7 antibody or the extracellular peptide of Fzd7 (soluble Fzd7 peptide) displayed anti-cancer activity in vitro and in vivo mainly due to the inhibition of the canonical Wnt signaling pathway. Furthermore, pharmacological inhibition of Fzd7 by small interfering peptides or a small molecule inhibitor suppressed β-catenin-dependent tumor cell growth. Therefore, targeted inhibition of Fzd7 represents a rational and promising new approach for cancer therapy.

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“…The SFRP are soluble glycoproteins that inhibit the Wnt pathway by sequestering Wnt proteins, thus preventing their interaction with Fzd receptors. There are other Wnt inhibitors like WIF or Soggy1 (Filipovich et al, 2011; Figure 3). The physiological role of these proteins is to inhibit the Wnt pathway in a time and tissue-specific manner both during development and in adult tissues.…”

Section: Wnt Signalingmentioning

confidence: 99%

Role of the Wnt Pathway in Thyroid Cancer

Sastre-Perona¹,

Santisteban²

2012

Front. Endocrin.

107

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Aberrant activation of Wnt signaling is involved in the development of several epithelial tumors. Wnt signaling includes two major types of pathways: (i) the canonical or Wnt/β-catenin pathway; and (ii) the non-canonical pathways, which do not involve β-catenin stabilization. Among these pathways, the Wnt/β-catenin pathway has received most attention during the past years for its critical role in cancer. A number of publications emphasize the role of the Wnt/β-catenin pathway in thyroid cancer. This pathway plays a crucial role in development and epithelial renewal, and components such as β-catenin and Axin are often mutated in thyroid cancer. Although it is accepted that altered Wnt signaling is a late event in thyroid cell transformation that affects anaplastic thyroid tumors, recent data suggest that it is also altered in papillary thyroid carcinoma (PTC) with RET/PTC mutations. Therefore, the purpose of this review is to summarize the main relevant data of Wnt signaling in thyroid cancer, with special emphasis on the Wnt/β-catenin pathway.

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Physiological inhibitors of Wnt signaling

Cited by 28 publications

References 144 publications

Astragaloside IV Inhibits the Up-Regulation of Wnt/β-Catenin Signaling in Rats with Unilateral Ureteral Obstruction

Astragaloside IV Inhibits the Up-Regulation of Wnt/β-Catenin Signaling in Rats with Unilateral Ureteral Obstruction

Frizzled7 as an emerging target for cancer therapy

Role of the Wnt Pathway in Thyroid Cancer

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