Article (Scientific journals)
DUSP3/VHR is a pro-angiogenic atypical dual-specificity phosphatase
Amand, Mathieu; Erpicum, Charlotte; BAJOU, Khalid et al.
2014In Molecular Cancer
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Abstract :
[en] Background DUSP3 phosphatase, also known as Vaccinia-H1 Related (VHR) phosphatase, encoded by DUSP3/Dusp3 gene, is a relatively small member of the dual-specificity protein phosphatases. In vitro studies showed that DUSP3 is a negative regulator of ERK and JNK pathways in several cell lines. On the other hand, DUSP3 is implicated in human cancer. It has been alternatively described as having tumor suppressive and oncogenic properties. Thus, the available data suggest that DUSP3 plays complex and contradictory roles in tumorigenesis that could be cell type-dependent. Since most of these studies were performed using recombinant proteins or in cell-transfection based assays, the physiological function of DUSP3 has remained elusive. Results Using immunohistochemistry on human cervical sections, we observed a strong expression of DUSP3 in endothelial cells (EC) suggesting a contribution for this phosphatase to EC functions. DUSP3 downregulation, using RNA interference, in human EC reduced significantly in vitro tube formation on Matrigel and spheroid angiogenic sprouting. However, this defect was not associated with an altered phosphorylation of the documented in vitro DUSP3 substrates, ERK1/2, JNK1/2 and EGFR but was associated with an increased PKC phosphorylation. To investigate the physiological function of DUSP3, we generated Dusp3-deficient mice by homologous recombination. The obtained DUSP3-/- mice were healthy, fertile, with no spontaneous phenotype and no vascular defect. However, DUSP3 deficiency prevented neo-vascularization of transplanted b-FGF containing Matrigel and LLC xenograft tumors as evidenced by hemoglobin (Hb) and FITC-dextran quantifications. Furthermore, we found that DUSP3 is required for b-FGF-induced microvessel outgrowth in the aortic ring assay. Conclusions All together, our data identify DUSP3 as a new important player in angiogenesis.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Author, co-author :
Amand, Mathieu ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Erpicum, Charlotte ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
BAJOU, Khalid ;  Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
Cerignoli, fabio
Blacher, Silvia ;  Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
Martin, Maud ;  Université de Liège - ULiège > GIGA-Research
Dequiedt, Franck  ;  Université de Liège - ULiège > GIGA-Research
Drion, Pierre ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R:Méth. expér.des anim. de labo et éth. en expér. anim.
Singh, Pratibha
Zurashvili, Tinatin ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Vandereyken, Maud ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Musumeci, Lucia ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Mustelin, Tomas
Moutschen, Michel  ;  Centre Hospitalier Universitaire de Liège - CHU > Maladies infectieuses et médecine interne générale
Gilles, Christine ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Noël, Agnès ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Rahmouni, Souad  ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
More authors (7 more) Less
Language :
English
Title :
DUSP3/VHR is a pro-angiogenic atypical dual-specificity phosphatase
Publication date :
2014
Journal title :
Molecular Cancer
eISSN :
1476-4598
Publisher :
BioMed Central, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 15 May 2014

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