Current drug design to target the Semaphorin/Neuropilin/Plexin complexes

Meyer, Lionel; Fritz, Justine; Pierdant-Mancera, Marie; Bagnard, Dominique

doi:10.1080/19336918.2016.1261785

Cited by 32 publications

(21 citation statements)

References 86 publications

(66 reference statements)

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“…The aim of this study was to investigate the role of Sema5A [ 1 , 44 ], in melanoma progression and to dissect the molecular mechanisms regulating its expression.…”

Section: Discussionmentioning

confidence: 99%

Semaphorin 5A drives melanoma progression: role of Bcl-2, miR-204 and c-Myb

D’Aguanno

Valentini

Tupone

et al. 2018

J Exp Clin Cancer Res

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BackgroundMelanoma, the most aggressive form of skin cancer, is characterized by high rates of metastasis, drug resistance and mortality. Here we investigated the role of Semaphorin 5A (Sema5A) on the properties associated with melanoma progression and the factors involved in Sema5A regulation.MethodsWestern blotting, qRT-PCR, Chromatin immunoprecipitation (ChIP) assay, immunohistochemistry of melanoma patient specimens and xenograft tissues, in vitro Transwell assay for cell migration and invasion evaluation, in vitro capillary-like structure formation analysis.ResultsA significant correlation of Sema5A mRNA expression and melanoma progression was observed by analyzing GEO profile dataset. Endogenous Sema5A protein was detected in 95% of human melanoma cell lines tested, in 70% of metastatic specimens from patients affected by melanoma, and 16% of in situ melanoma specimens showed a focal positivity. We demonstrated that Sema5A regulates in vitro cell migration and invasion and the formation of vasculogenic structures. We also found an increase of Sema5A at both mRNA and protein level after forced expression of Bcl-2. By use of transcriptional and proteasome inhibitors, we showed that Bcl-2 increases the stability of Sema5A mRNA and protein. Moreover, by ChIP we demonstrated that Sema5A expression is under the control of the transcription factor c-Myb and that c-Myb recruitment on Sema5A promoter is increased after Bcl-2 overexpression. Finally, a concomitant decrease in the expression of Sema5A, Bcl-2 and c-Myb proteins was observed in melanoma cells after miR-204 overexpression.ConclusionOverall our data provide evidences supporting the role of Sema5A in melanoma progression and the involvement of Bcl-2, miR-204 and c-Myb in regulating its expression.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0933-x) contains supplementary material, which is available to authorized users.

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“…The aim of this study was to investigate the role of Sema5A [ 1 , 44 ], in melanoma progression and to dissect the molecular mechanisms regulating its expression.…”

Section: Discussionmentioning

confidence: 99%

Semaphorin 5A drives melanoma progression: role of Bcl-2, miR-204 and c-Myb

D’Aguanno

Valentini

Tupone

et al. 2018

J Exp Clin Cancer Res

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“…Growth cones were present in the odontoblast layer of molars at PN7 but not in the case of cell reassociations implanted in “Nude” mice or at PN0 (Kökten, Lesot, & Kuchler‐Bopp, ). The semaphorin/neuropilin/plexin complex has been shown as key molecular system for drug design (Meyer, Fritz, Pierdant‐Mancera, & Bagnard, ). Selective inhibitor of Sema3A, SM‐345431 (Vinaxanthone), or SM‐216289 (Xanthofulvin) showed interesting therapeutic potential in the treatment of spinal cord injury or in promoting the regeneration of peripheral nerves in a mouse corneal transplantation model, respectively (Kaneko et al, ; Omoto et al, ).…”

Section: Discussionmentioning

confidence: 99%

Semaphorin 3A receptor inhibitor as a novel therapeutic to promote innervation of bioengineered teeth

Kuchler‐Bopp

Bagnard

Van‐Der‐Heyden

et al. 2018

J Tissue Eng Regen Med

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The sensory innervation of the dental pulp is essential for tooth function and protection. It is mediated by axons originating from the trigeminal ganglia and is spatio-temporally regulated. We have previously shown that the innervation of bioengineered teeth can be achieved only under immunosuppressive conditions. The aim of this study was to develop a model to determine the role of Semaphorin 3A (Sema3A) in the innervation of bioengineered teeth. We first analysed innervation of the dental pulp of mandibular first molars in newborn (postnatal day 0: PN0) mice deficient for Sema3A (Sema3A ), a strong inhibitor of axon growth. While at PN0, axons detected by immunostaining for peripherin and NF200 were restricted to the peridental mesenchyme in Sema3A mice, they entered the dental pulp in Sema3A mice. Then, we have implanted cultured teeth obtained from embryonic day-14 (E14) molar germs of Sema3A mice together with trigeminal ganglia. The dental pulps of E14 cultured and implanted Sema3A teeth were innervated, whereas the axons did not enter the pulp of E14 Sema3A cultured and implanted teeth. A "Membrane Targeting Peptide NRP1," suppressing the inhibitory effect of Sema3A, has been previously identified. The injection of this peptide at the site of implantation allowed the innervation of the dental pulp of bioengineered teeth obtained from E14 dental dissociated mesenchymal and epithelial cells reassociations of ICR mice. In conclusion, these data show that inhibition of only one axon repellent molecule, Sema3A, allows for pulp innervation of bioengineered teeth.

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“…Both neuropilins and plexins have been implicated in cancer (reviewed in [ 7 , 8 , 72 , 73 , 74 ]). As Sema3C signaling has been implicated in GSC maintenance, we will focus our discussion on its receptors in glioblastoma.…”

Section: Sema3c Receptors In Carcinogenesismentioning

confidence: 99%

“…The quest to develop small molecule inhibitors targeting Sema3C or its receptors has not yet been fruitful [ 73 ]. However, specific inhibitors of Sema3A, xanthofulvin and vinaxanthone, have been isolated from the broth of fermented fungus [ 94 , 95 , 96 ].…”

Section: Therapeutic Strategies Targeting Sema3c and Its Receptorsmentioning

confidence: 99%

Semaphorin 3C and Its Receptors in Cancer and Cancer Stem-Like Cells

Hao

2018

Biomedicines

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Neurodevelopmental programs are frequently dysregulated in cancer. Semaphorins are a large family of guidance cues that direct neuronal network formation and are also implicated in cancer. Semaphorins have two kinds of receptors, neuropilins and plexins. Besides their role in development, semaphorin signaling may promote or suppress tumors depending on their context. Sema3C is a secreted semaphorin that plays an important role in the maintenance of cancer stem-like cells, promotes migration and invasion, and may facilitate angiogenesis. Therapeutic strategies that inhibit Sema3C signaling may improve cancer control. This review will summarize the current research on the Sema3C pathway and its potential as a therapeutic target.

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Current drug design to target the Semaphorin/Neuropilin/Plexin complexes

Cited by 32 publications

References 86 publications

Semaphorin 5A drives melanoma progression: role of Bcl-2, miR-204 and c-Myb

Semaphorin 5A drives melanoma progression: role of Bcl-2, miR-204 and c-Myb

Semaphorin 3A receptor inhibitor as a novel therapeutic to promote innervation of bioengineered teeth

Semaphorin 3C and Its Receptors in Cancer and Cancer Stem-Like Cells

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