2010

DOI: 10.1124/pr.110.002931

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International Union of Basic and Clinical Pharmacology. LXXX. The Class Frizzled Receptors

Gunnar Schulte¹

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Introduction2

Stratégie Utilisée Pour Purifier Le Récepteur Smo1

Anti-frizzled1

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Cited by 195 publications

(235 citation statements)

References 448 publications

(594 reference statements)

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“…It also regulates a plethora of processes during embryonic development, such as stem cell proliferation, migration, and differentiation. Dysfunction of WNT-FZD signaling leads to impairment of cell regulatory mechanisms, thereby leading to disease, such as cancer and neurological and bone disorders (1)(2)(3). Despite the physiological relevance of this pathway, little is known about the specificity of the interactions between the 19 members of the WNT family of lipoglycoproteins and their respective FZD cell-surface receptors.…”

mentioning

confidence: 99%

Systematic Mapping of WNT-FZD Protein Interactions Reveals Functional Selectivity by Distinct WNT-FZD Pairs

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,

²

,

et al. 2015

Journal of Biological Chemistry

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Background: WNT-FZD specificity and signaling outcome have not been systematically mapped so far. Results: WNTs show selective binding to FZDs, and respective WNT-FZD pairs exert functional selectivity in different downstream signaling pathways. Conclusion: The WNT-FZD signaling system provides ligand-receptor selectivity. Significance: Understanding WNT-FZD selectivity is crucial for development of WNT pathway inhibitors and further understanding of molecular interactions within the WNT receptor signaling complex.

“…It also regulates a plethora of processes during embryonic development, such as stem cell proliferation, migration, and differentiation. Dysfunction of WNT-FZD signaling leads to impairment of cell regulatory mechanisms, thereby leading to disease, such as cancer and neurological and bone disorders (1)(2)(3). Despite the physiological relevance of this pathway, little is known about the specificity of the interactions between the 19 members of the WNT family of lipoglycoproteins and their respective FZD cell-surface receptors.…”

mentioning

confidence: 99%

Systematic Mapping of WNT-FZD Protein Interactions Reveals Functional Selectivity by Distinct WNT-FZD Pairs

¹

,

²

,

et al. 2015

Journal of Biological Chemistry

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Background: WNT-FZD specificity and signaling outcome have not been systematically mapped so far. Results: WNTs show selective binding to FZDs, and respective WNT-FZD pairs exert functional selectivity in different downstream signaling pathways. Conclusion: The WNT-FZD signaling system provides ligand-receptor selectivity. Significance: Understanding WNT-FZD selectivity is crucial for development of WNT pathway inhibitors and further understanding of molecular interactions within the WNT receptor signaling complex.

“…L'homologie faible avec les autres classes de récepteurs couplés aux protéines G (RCPG) a conduit à classifier ces récepteurs dans la classe F des RCPG [14] (➜). Cependant, l'appartenance du récepteur Smo à la famille des RCPG demeurait controversée avant sa cristallisation.…”

Section: Stratégie Utilisée Pour Purifier Le Récepteur Smounclassified

Structure du récepteur Smoothened

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,

Hoch²,

et al. 2013

Med Sci (Paris)

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“…The Frizzled (FZD) family of transmembrane G protein-coupled receptors consists of 10 members (FZD 1-10), which are activated by secreted lipoglycoproteins of the Wnt family [177]. The highly conserved Wnt/FZD signaling pathway has multiple functions in animal development and cell fate determination and polarization [178].…”

Section: Anti-frizzledmentioning

confidence: 99%

Targeting Human Cancer Stem Cells with Monoclonal Antibodies

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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