Yellow submarine of the Wnt/Frizzled signaling: Submerging from the G protein harbor to the targets

Koval, Alexey; Purvanov, Vladimir; Egger-Adam, Diane; Katanaev, Vladimir L.

doi:10.1016/j.bcp.2011.06.005

Cited by 63 publications

(51 citation statements)

References 170 publications

(242 reference statements)

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“…The mechanisms involved in Ca 2+ overload require to be fully elucidated, and mitochondrial dysfunction, an increase in cell membrane permeability, and catecholamine are currently the primary known causes of Ca 2+ overload (4,35,36). The Wnt5a/Frizzled-2 pathway, which is a well-known Ca 2+ -modulating pathway, is activated upon inflammation or ischemia/anoxia stimulation (37,38). A previous study by our group proved that the Wnt5a/Frizzled-2 pathway has a vital role in Ca 2+ release in H/R cardiomyocytes (15).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol attenuates hypoxia/reoxygenation-induced Ca2+ overload by inhibiting the Wnt5a/Frizzled-2 pathway in rat H9c2 cells

Zhou

Zhu

et al. 2014

Molecular Medicine Reports

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Abstract.Resveratrol is able to protect myocardial cells from ischemia/reperfusion-induced injury. However, the mechanism has yet to be fully elucidated. In the present study, it is reported that resveratrol has a critical role in the control of Ca 2+ overload, which is the primary underlying cause of ischemia/reperfusion injury. Hypoxia/reoxygenation (H/R) treatment decreased the cell viability and increased the apoptosis of H9c2 cells, whereas the caspase-3 and intracellular Ca 2+ levels were greatly elevated compared with the control group. Treatment of H9c2 cells with resveratrol (5, 15 and 30 µM) reduced caspase-3 expression and cardiomyocyte apoptosis in a dose-dependent manner, and the intracellular Ca 2+ overload was also significantly decreased. Furthermore, Frizzled-2 and Wnt5a belong to the non-canonical Wnt/Ca 2+ pathway, which have been demonstrated to be responsible for Ca 2+ overload, and were thus detected in the present study. The results indicated that both the mRNA and protein expression levels of Frizzled-2 and Wnt5a in H/R-induced H9c2 cells were markedly increased compared with the levels found in normal cells, and treatment with resveratrol (5, 15 and 30 µM) significantly reduced the expression of Frizzled-2 and Wnt5a compared with the H/R group. The results indicated that resveratrol protected myocardial cells from H/R injury by inhibiting the Ca 2+ overload through suppression of the Wnt5a/Frizzled-2 pathway.

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Section: Discussionmentioning

confidence: 99%

Resveratrol attenuates hypoxia/reoxygenation-induced Ca2+ overload by inhibiting the Wnt5a/Frizzled-2 pathway in rat H9c2 cells

Zhou

Zhu

et al. 2014

Molecular Medicine Reports

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“…Although the current HTS efforts are dominated by the usage of transcription-based assays, it is our conviction that readouts focusing on the more upstream events of the pathway are in urgent demand. These readouts largely exploit the emerging GPCR properties of FZD proteins, the feature for the long time undervalued by Wnt researchers [43]. Embracing FZDs as part of the GPCR superfamily arms the field with the vast inventory of the GPCR-targeting drug discovery approaches [42,61].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, internalization of activated FZD proteins is utilized in different Wnt pathways and involves early transducers, making it amenable for screening with the focus on the early signaling events [43,62]. In most cases internalization of a GPCR leads to attenuation of the signal.…”

Section: High-content Screening For Wnt-fzd Signalingmentioning

confidence: 99%

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Platforms for high-throughput screening of Wnt/Frizzled antagonists

Koval

Katanaev

2012

Drug Discovery Today

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“…The highly conserved Wnt/FZD signaling pathway has multiple functions in animal development and cell fate determination and polarization [178]. Deregulation of the Wnt pathway and up-regulation of FZD receptors play important roles in tumorigenesis and CSC maintenance that is observed in a variety of human cancers, including colorectal cancer, hepatocellular carcinoma and triple-negative breast cancer [164,[178][179][180][181].…”

Section: Anti-frizzledmentioning

confidence: 99%

Targeting Human Cancer Stem Cells with Monoclonal Antibodies

Naujokat¹

2012

J Clin Cell Immunol

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Cancer stem cells (CSCs) constitute a distinct subpopulation of tumor cells that exhibit self-renewal and tumor initiation capacity and the ability to give rise to the heterogenous lineages of cancer cells that comprise the tumor. CSCs possess various intrinsic mechanisms of resistance to conventional chemotherapeutics, novel tumor-targeted drugs and radiation therapy, permitting them to survive current cancer therapies and to initiate tumor recurrence and metastasis. Different cell surface and transmembrane proteins expressed by CSCs, including CD44, CD47, EpCAM (CD326), CD123, CD133, GD2, Lgr5, insulin-like growth factor receptor I (IGF-IR), and members of the Notch and Wnt signaling pathways, have been identified and mainly used for the characterization of CSCs in experimental settings. Recently, monoclonal antibodies and antibody constructs such as Triomabs and BiTEs raised against these CSC proteins have shown efficacy against CSCs in human xenograft mice, and some of them have been demonstrated to induce tumor regression in clinical trials.Since current cancer therapies fail to eliminate CSCs, ultimately leading to cancer recurrence and progression, selective targeting of CSCs with mAbs and antibody constructs reviewed herein may represent a novel and promising therapeutic strategy to eradicate cancer.

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Yellow submarine of the Wnt/Frizzled signaling: Submerging from the G protein harbor to the targets

Cited by 63 publications

References 170 publications

Resveratrol attenuates hypoxia/reoxygenation-induced Ca2+ overload by inhibiting the Wnt5a/Frizzled-2 pathway in rat H9c2 cells

Resveratrol attenuates hypoxia/reoxygenation-induced Ca2+ overload by inhibiting the Wnt5a/Frizzled-2 pathway in rat H9c2 cells

Platforms for high-throughput screening of Wnt/Frizzled antagonists

Targeting Human Cancer Stem Cells with Monoclonal Antibodies

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