Syndecan-1 alters heparan sulfate composition and signaling pathways in malignant mesothelioma.

Abstract : Syndecan-1 is a proteoglycan that acts as co-receptor through its heparan sulfate (HS) chains and plays important roles in cancer. HS chains are highly variable in length and sulfation pattern. This variability is enhanced by the SULF1/2 enzymes, which remove 6-O-sulfates from HS. We used malignant mesothelioma, an aggressive tumor with poor prognosis, as a model and demonstrated that syndecan-1 over-expression down-regulates SULF1 and alters the HS biosynthetic machinery. Biochemical characterization revealed a 2.7-fold reduction in HS content upon syndecan-1 over-expression, but an overall increase in sulfation. Consistent with low SULF1 levels, trisulfated disaccharides increased 2.5-fold. ERK1/2 activity was enhanced 6-fold. Counteracting ERK activation, Akt, WNK1, and c-Jun were inhibited. The net effect of these changes manifested in G1 cell cycle arrest. Studies of pleural effusions showed that SULF1 levels are lower in pleural malignancies compared to benign conditions and inversely correlate with the amounts of syndecan-1, suggesting important roles for syndecan-1 and SULF1 in malignant mesothelioma.
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Article dans une revue
Cellular Signalling, Elsevier, 2015, 27 (10), pp.2054-67
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http://hal.univ-grenoble-alpes.fr/hal-01199253
Contributeur : Frank Thomas <>
Soumis le : mardi 15 septembre 2015 - 10:51:32
Dernière modification le : lundi 19 février 2018 - 14:34:03

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  • HAL Id : hal-01199253, version 1
  • PUBMED : 26210886

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Ghazal Heidari-Hamedani, Romain R Vivès, Amal Seffouh, Nikolaos A Afratis, Arie Oosterhof, et al.. Syndecan-1 alters heparan sulfate composition and signaling pathways in malignant mesothelioma.. Cellular Signalling, Elsevier, 2015, 27 (10), pp.2054-67. 〈hal-01199253〉

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