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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2022 | Breast Cancer | Research

Elevated transcription and glycosylation of B3GNT5 promotes breast cancer aggressiveness

Authors: Zhaorui Miao, Qianhua Cao, Ruocen Liao, Xingyu Chen, Xiaoli Li, Longchang Bai, Chenglong Ma, Xinyue Deng, Zhijun Dai, Jun Li, Professor Chenfang Dong

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2022

Abstract

Background

Basal-like breast cancer (BLBC) is the most aggressive subtype of breast cancer because of its aggressive biological characteristics and no effective targeted agents. However, the mechanism underlying its aggressive behavior remain poorly understood. β1,3-N-acetylglucosaminyltransferase V (B3GNT5) overexpression occurs specifically in BLBC. Here, we studied the possible molecular mechanisms of B3GBT5 promoting the aggressiveness of BLBC.

Methods

The potential effects of B3GNT5 on breast cancer cells were tested by colony formation, mammosphere formation, cell proliferation assay, flow cytometry and Western blotting. The glycosylation patterns of B3GNT5 and associated functions were determined by Western blotting, quantitative real-time PCR and flow cytometry. The effect of B3GNT5 expression on BLBC was assessed by in vitro and in vivo tumorigenesis model.

Results

In this study, we showed that B3GNT5 copy number amplification and hypomethylation of B3GNT5 promoter contributed to the overexpression of B3GNT5 in BLBC. Knockout of B3GNT5 strongly reduced surface expression of SSEA-1 and impeded cancer stem cell (CSC)-like properties of BLBC cells. Our results also showed that B3GNT5 protein was heavily N-glycosylated, which is critical for its protein stabilization. Clinically, elevated expression of B3GNT5 was correlated with high grade, large tumor size and poor survival, indicating poor prognosis of breast cancer patients.

Conclusions

Our work uncovers the critical association of B3GNT5 overexpression and glycosylation with enhanced CSCs properties in BLBC. These findings suggest that B3GNT5 has the potential to become a prognostic marker and therapeutic target for BLBC.

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Title: Elevated transcription and glycosylation of B3GNT5 promotes breast cancer aggressiveness
Authors: Zhaorui Miao
Qianhua Cao
Ruocen Liao
Xingyu Chen
Xiaoli Li
Longchang Bai
Chenglong Ma
Xinyue Deng
Zhijun Dai
Jun Li
Professor Chenfang Dong
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2022
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-022-02375-5

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