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Breast Cancer Research
Published in: Breast Cancer Research 1/2021

01-12-2021 | Metastasis | Research article

High B3GALT5 expression confers poor clinical outcome and contributes to tumor progression and metastasis in breast cancer

Authors: Yu-Mei Liao, Ya-Hui Wang, Jung-Tung Hung, Yu-Ju Lin, Yen-Lin Huang, Guo-Shiou Liao, Ya-Ling Hsu, Jen-Chien Wu, Alice L. Yu

Published in: Breast Cancer Research | Issue 1/2021

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Abstract

Background

Existence of breast cancer stem cells (BCSCs) is implicated in disease relapse, metastasis, and resistance of treatment. β1,3-Galactosyltransferase 5 (B3GALT5) has been shown to be a pro-survival marker for BCSCs. However, little is known about the prognostic significance of B3GALT5 in breast cancer.

Methods

Paired tissues (tumor part and adjacent non-tumor part) from a cohort of 202 women with breast cancer were used to determine the expression levels of B3GALT5 mRNA by qRT-PCR. Kaplan–Meier and multivariable Cox proportional hazard models were used to assess survival differences in terms of relapse-free survival (RFS) and overall survival (OS). Both breast cancer cells and cancer stem cells (BCSCs) were used to see the in vitro effects of knockdown or overexpression of B3GALT5 on cell migration, invasion, and epithelial-to-mesenchymal transition (EMT). A patient-derived xenograft (PDX) model was used to see the in vivo effects of knockdown of B3GALT5 in BCSCs on tumor growth and metastasis.

Results

Higher expression of B3GALT5 in 202 breast cancer tissues, especially in adjacent non-tumor tissue, correlated with poor clinical outcomes including shorter OS and RFS in all patients, especially those with early stage breast cancer. In vitro studies showed B3GALT5 could enhance cell migration, invasion, mammosphere formation, and EMT. Of note, B3GALT5 upregulated the expression of β-catenin and EMT activator zinc finger E-box binding homeobox 1 (ZEB1) pathway in BCSCs. In vivo studies showed B3GALT5 expression in BCSCs is critical for not only tumor growth but also lymph node and lung metastasis in PDX mice.

Conclusion

Our results demonstrated the value of B3GALT5 as a prognostic marker of breast cancer, especially among the early stage patients, and its crucial roles in regulating EMT, cell migration, and stemness thereby promoting breast cancer progression.
Appendix
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Metadata
Title
High B3GALT5 expression confers poor clinical outcome and contributes to tumor progression and metastasis in breast cancer
Authors
Yu-Mei Liao
Ya-Hui Wang
Jung-Tung Hung
Yu-Ju Lin
Yen-Lin Huang
Guo-Shiou Liao
Ya-Ling Hsu
Jen-Chien Wu
Alice L. Yu
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2021
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-020-01381-9

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