EMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha mediated up-regulation of VEGF-receptor-2.
EMMPRIN's expression in melanoma tissue was reported to be predictive of poor prognosis. Here we demonstrate that EMMPRIN up-regulated VEGF receptor-2 (VEGFR-2) in two different primary melanoma cell lines and consequently increased migration and proliferation of these cells while inhibiting th...
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2010
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oai:doaj.org-article:aa0e8ff42c2e47909ed21d481416828f2021-11-18T06:35:35ZEMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha mediated up-regulation of VEGF-receptor-2.1932-620310.1371/journal.pone.0012265https://doaj.org/article/aa0e8ff42c2e47909ed21d481416828f2010-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20824203/?tool=EBIhttps://doaj.org/toc/1932-6203EMMPRIN's expression in melanoma tissue was reported to be predictive of poor prognosis. Here we demonstrate that EMMPRIN up-regulated VEGF receptor-2 (VEGFR-2) in two different primary melanoma cell lines and consequently increased migration and proliferation of these cells while inhibiting their apoptosis. SiRNA inhibition of VEGFR-2 expression abrogated these EMMPRIN effects. EMMPRIN regulation of VEGFR-2 was mediated through the over-expression of HIF-2alpha and its translocation to the nucleus where it forms heterodimers with HIF-1beta. These results were supported by an in vivo correlation between the expression of EMMPRIN with that of VEGFR-2 in human melanoma tissues as well as with the extent of HIF-2alpha localization in the nucleus. They demonstrate a novel mechanism by which EMMPRIN promotes tumor progression through HIF-2alpha/VEGFR-2 mediated mechanism, with an autocrine role in melanoma cell malignancy. The inhibition of EMMPRIN in cancer may thus simultaneously target both the VEGFR-2/VEGF system and the matrix degrading proteases to block tumor cell growth and invasion.Faten BougatefSuzanne MenashiFarah KhayatiBenyoussef NaïmiRaphaël PorcherMarie-Pierre PodgorniakGuy MillotAnne JaninFabien CalvoCéleste LebbéSamia MourahPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 8, p e12265 (2010) |
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Medicine R Science Q Faten Bougatef Suzanne Menashi Farah Khayati Benyoussef Naïmi Raphaël Porcher Marie-Pierre Podgorniak Guy Millot Anne Janin Fabien Calvo Céleste Lebbé Samia Mourah EMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha mediated up-regulation of VEGF-receptor-2. |
| description |
EMMPRIN's expression in melanoma tissue was reported to be predictive of poor prognosis. Here we demonstrate that EMMPRIN up-regulated VEGF receptor-2 (VEGFR-2) in two different primary melanoma cell lines and consequently increased migration and proliferation of these cells while inhibiting their apoptosis. SiRNA inhibition of VEGFR-2 expression abrogated these EMMPRIN effects. EMMPRIN regulation of VEGFR-2 was mediated through the over-expression of HIF-2alpha and its translocation to the nucleus where it forms heterodimers with HIF-1beta. These results were supported by an in vivo correlation between the expression of EMMPRIN with that of VEGFR-2 in human melanoma tissues as well as with the extent of HIF-2alpha localization in the nucleus. They demonstrate a novel mechanism by which EMMPRIN promotes tumor progression through HIF-2alpha/VEGFR-2 mediated mechanism, with an autocrine role in melanoma cell malignancy. The inhibition of EMMPRIN in cancer may thus simultaneously target both the VEGFR-2/VEGF system and the matrix degrading proteases to block tumor cell growth and invasion. |
| format |
article |
| author |
Faten Bougatef Suzanne Menashi Farah Khayati Benyoussef Naïmi Raphaël Porcher Marie-Pierre Podgorniak Guy Millot Anne Janin Fabien Calvo Céleste Lebbé Samia Mourah |
| author_facet |
Faten Bougatef Suzanne Menashi Farah Khayati Benyoussef Naïmi Raphaël Porcher Marie-Pierre Podgorniak Guy Millot Anne Janin Fabien Calvo Céleste Lebbé Samia Mourah |
| author_sort |
Faten Bougatef |
| title |
EMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha mediated up-regulation of VEGF-receptor-2. |
| title_short |
EMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha mediated up-regulation of VEGF-receptor-2. |
| title_full |
EMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha mediated up-regulation of VEGF-receptor-2. |
| title_fullStr |
EMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha mediated up-regulation of VEGF-receptor-2. |
| title_full_unstemmed |
EMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha mediated up-regulation of VEGF-receptor-2. |
| title_sort |
emmprin promotes melanoma cells malignant properties through a hif-2alpha mediated up-regulation of vegf-receptor-2. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/aa0e8ff42c2e47909ed21d481416828f |
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