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Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

RPN2-mediated glycosylation of tetraspanin CD63 regulates breast cancer cell malignancy

Authors: Naoomi Tominaga, Keitaro Hagiwara, Nobuyoshi Kosaka, Kimi Honma, Hitoshi Nakagama, Takahiro Ochiya

Published in: Molecular Cancer | Issue 1/2014

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Abstract

Background

The tetraspanin CD63 is a highly N-glycosylated protein that is known to regulate cancer malignancy. However, the contribution of glycosylation of CD63 to cancer malignancy remains unclear. Previously, we reported that ribophorin II (RPN2), which is part of an N-oligosaccharyle transferase complex, is responsible for drug resistance in breast cancer cells. In this study, we demonstrate that cancer malignancy associated with the glycosylation of CD63 is regulated by RPN2.

Results

Inhibition of RPN2 expression led to a reduction in CD63 glycosylation. In addition, the localization of CD63 was deregulated by knockdown of RPN2. Interestingly, multidrug resistance protein 1 (MDR1) localization was displaced from the cell surface in CD63-silenced cells. CD63 silencing reduced the chemoresistance and invasion ability of malignant breast cancer cells. Furthermore, the enrichment of CD63/MDR1-double positive cells was associated with lymph node metastasis. Taken together, these results indicated that high glycosylation of CD63 by RPN2 is implicated in clinical outcomes in breast cancer patients.

Conclusions

These findings describe a novel and important function of RPN2-mediated CD63 glycosylation, which regulates MDR1 localization and cancer malignancy, including drug resistance and invasion.
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Metadata
Title
RPN2-mediated glycosylation of tetraspanin CD63 regulates breast cancer cell malignancy
Authors
Naoomi Tominaga
Keitaro Hagiwara
Nobuyoshi Kosaka
Kimi Honma
Hitoshi Nakagama
Takahiro Ochiya
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-134

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