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Granulin-epithelin precursor interacts with heparan sulfate on liver cancer cells.


ABSTRACT: Granulin-epithelin precursor (GEP) is a pluripotent secretory growth factor which promotes cancer progression in a number of human cancers. However, how cancer cells interact with GEP remains unknown. In this study, we aimed to identify the cell surface-binding partner of GEP on liver cancer cells. Human recombinant GEP (rGEP) was expressed and purified to homogeneity. The rGEP was shown to trigger phosphorylation of AKT and ERK1/2 in liver cancer cells. We demonstrated cell surface attachment of rGEP, which was blocked by prebinding of platelet-derived growth factor-AA, platelet-derived growth factor-BB and fibroblast growth factor-2. Therefore, heparan sulfate (HS) had been reasoned as the binding partner of rGEP. Heparinase digestion validated the role of HS on supporting the attachment. The heparin-binding domain of GEP was mapped to RRH(555-557) in the C-terminal region. Suppression of the HS polymerase exostosin-1 reduced the rGEP binding and rGEP-mediated signaling transduction. Suppression of a specific HS proteoglycan, glypican-3, also showed a partial reduction of rGEP binding and an inhibition on rGEP-mediated activation of AKT. Furthermore, glypican-3 was shown to correlate with the expressions of GEP in clinical samples (Spearman's ? = 0.363, P = 0.001). This study identified HS, partly through glypican-3, as a novel binding partner of GEP on the surface of liver cancer cells.

SUBMITTER: Yip CW 

PROVIDER: S-EPMC4216055 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Granulin-epithelin precursor interacts with heparan sulfate on liver cancer cells.

Yip Chi Wai CW   Cheung Phyllis F Y PF   Leung Idy C Y IC   Wong Nicholas C L NC   Cheng Christine K C CK   Fan Sheung Tat ST   Cheung Siu Tim ST  

Carcinogenesis 20140812 11


Granulin-epithelin precursor (GEP) is a pluripotent secretory growth factor which promotes cancer progression in a number of human cancers. However, how cancer cells interact with GEP remains unknown. In this study, we aimed to identify the cell surface-binding partner of GEP on liver cancer cells. Human recombinant GEP (rGEP) was expressed and purified to homogeneity. The rGEP was shown to trigger phosphorylation of AKT and ERK1/2 in liver cancer cells. We demonstrated cell surface attachment o  ...[more]

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