The RET receptor: function in development and dysfunction in congenital malformation

Manié, Serge N.; Santoro, Massimo; Fusco, Alfredo; Billaud, Marc

doi:10.1016/s0168-9525(01)02420-9

Cited by 261 publications

(226 citation statements)

References 70 publications

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“…In addition, ligand binding has been proposed to have other structural effects, such as receptor multimerization. In fact, with the exception of Ptc and integrins, most DRs display homo-multimerization properties in the presence of their respective ligand Manie et al, 2001;Stein et al, 2001;Mille et al, 2009a). Initially described as being important for positive signaling, receptor multimerization also seems to have a role in blocking apoptosis induction.…”

Section: Role Of Ligand Bindingmentioning

confidence: 99%

Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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Dependence receptors (DRs) now form a family of more than a dozen membrane receptors that are not linked by their structure, but by common functional traits. The most notable is their ability to trigger two opposite signaling pathways: in the presence of ligand, these receptors activate classic signaling pathways implicated in cell survival, migration and differentiation. In the absence of ligand, they do not stay inactive, rather they elicit an apoptotic signal. Thus, cells expressing this kind of receptor are dependent on the presence of ligand in the extracellular environment to survive. This review will recapitulate the increasing data regarding the molecular mechanisms associated with DRs, their potential implication during development, as well as their deregulation during tumorigenesis and, finally, their emergence as new possible therapeutic targets for cancer treatment.

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Section: Role Of Ligand Bindingmentioning

confidence: 99%

Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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“…The RET proto-oncogene encodes a transmembrane receptor of the tyrosine kinase family (Manie et al, 2001). It is expressed primarily in neural crest and urogenital precursor cells and is implicated in developmental processes, such as maturation of peripheral nervous system lineages, kidney morphogenesis or spermatogonia differentiation (Schuchardt et al, 1994;Durbec et al, 1996;Meng et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…The extracellular domain consists of four cadherin-like regions and a cysteinerich tract, which facilitates receptor dimerization upon ligand stimulation (Iwamoto et al, 1993;Takahashi et al, 1998). RET encodes three major proteins that arise through alternative splicing of the 3 0 -terminus, leading to expression of proteins that differ by their last 51 (RET51), 43 (RET43) or nine (RET9) amino acids, respectively (Manie et al, 2001). Among them, RET9 and RET51 are the major isoforms consisting of 1072 and 1114 amino acids, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…The signaling complex associated with RET9 markedly differs from RET51-associated factors, which might have an influence on the higher transforming potential of the RET51 isoform (Le Hir et al, 2000;Tsui-Pierchala et al, 2002). The RET receptor is activated through a multi-subunit complex involving a soluble ligand of the glial cell line-derived neurotrophic factor family and the appropriate glycosylphosphatidylinositol-anchored coreceptor (GFRa1-4) (Manie et al, 2001;Airaksinen and Saarma, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of potential mechanisms underlying genotype–phenotype correlations in multiple endocrine neoplasia type 2

et al. 2006

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“…4 Concise examination led to the detection of a striking genotype-phenotype correlation between the mutated RET codon and clinical manifestation of the disease, indicating that tumorigenesis and progression is conditioned by the type of mutation. 5,6 The most frequent mutation associated with the majority of MTC cases affects codon 634 in the cysteine-rich region of the extracellular domain of the receptor.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of systemic targeting of RET oncogene-based MTC with tumor-selective peptide-tagged Ad vectors in clinical mouse models

et al. 2011

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Significant advantage of targeted antitumoral treatment consists in the possibility to restrict maximum therapeutic efficacy to the malignant cell population by reducing toxicity in healthy tissues. Using different clinical models for aggressive medullary thyroid carcinoma (MTC), we have recently identified peptide ligands that bind highly selective to tumor cells. By linking the most convincing SRESPHP peptide to an adenoviral (Ad) vector expressing the MTC-related oncogene inhibitor RETDTK, gene transfer was specifically directed to neoplastic tissue after systemic virus administration. We show that peptide-mediated delivery of RETDTK significantly enhanced apoptosis, resulting in a strong inhibition of orthotopic and xenograft tumor growth. Conversely, tumors treated with controls expanded their initial size without notable cell death. According to the therapeutic effect, strong virus accumulation was found exclusively in thyroid carcinomas. Strikingly, application of native tropism depleted viral vector linked to tumor-selective peptide was accompanied by a substantial reduction of Ad binding to the liver. Of note, single systemic injection of a low dose (10e8 pfu/mouse) of MTC-specific Ad.RETDTK induced regression of multiple tumors at different sites in all treated animals. In sum, our results open up the possibility for an efficient cancer cell-specific therapy of primary MTC, their migrating populations and potentially metastases.

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The RET receptor: function in development and dysfunction in congenital malformation

Cited by 261 publications

References 70 publications

Dependence receptors: a new paradigm in cell signaling and cancer therapy

Dependence receptors: a new paradigm in cell signaling and cancer therapy

Evaluation of potential mechanisms underlying genotype–phenotype correlations in multiple endocrine neoplasia type 2

Evaluation of systemic targeting of RET oncogene-based MTC with tumor-selective peptide-tagged Ad vectors in clinical mouse models

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