Dataset Information

WSB-1 regulates the metastatic potential of hormone receptor negative breast cancer.

ABSTRACT:

Background

Metastatic spread is responsible for the majority of cancer-associated deaths. The tumour microenvironment, including hypoxia, is a major driver of metastasis. The aim of this study was to investigate the role of the E3 ligase WSB-1 in breast cancer biology in the context of the hypoxic tumour microenvironment, particularly regarding metastatic spread.

Methods

In this study, WSB-1 expression was evaluated in breast cancer cell lines and patient samples. In silico analyses were used to determine the impact of WSB-1 expression on distant metastasis-free survival (DMFS) in patients, and correlation between WSB1 expression and hypoxia gene expression signatures. The role of WSB-1 on metastasis promotion was evaluated in vitro and in vivo.

Results

High WSB1 expression was associated with decreased DMFS in ER-breast cancer and PR-breast cancer patients. Surprisingly, WSB1 expression was not positively correlated with known hypoxic gene expression signatures in patient samples. Our study is the first to show that WSB-1 knockdown led to decreased metastatic potential in breast cancer hormone receptor-negative models in vitro and in vivo. WSB-1 knockdown was associated with decreased metalloproteinase (MMP) activity, vascular endothelial growth factor (VEGF) secretion, and angiogenic potential.

Conclusions

Our data suggests that WSB-1 may be an important regulator of aggressive metastatic disease in hormone receptor-negative breast cancer. WSB-1 could therefore represent a novel regulator and therapeutic target for secondary breast cancer in these patients.

SUBMITTER: Poujade FA

PROVIDER: S-EPMC5943535 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Publications

WSB-1 regulates the metastatic potential of hormone receptor negative breast cancer.

Poujade Flore-Anne FA Mannion Aarren A Brittain Nicholas N Theodosi Andrew A Beeby Ellie E Leszczynska Katarzyna B KB Hammond Ester M EM Greenman John J Cawthorne Christopher C Pires Isabel M IM

British journal of cancer 20180315 9

<h4>Background</h4>Metastatic spread is responsible for the majority of cancer-associated deaths. The tumour microenvironment, including hypoxia, is a major driver of metastasis. The aim of this study was to investigate the role of the E3 ligase WSB-1 in breast cancer biology in the context of the hypoxic tumour microenvironment, particularly regarding metastatic spread.<h4>Methods</h4>In this study, WSB-1 expression was evaluated in breast cancer cell lines and patient samples. In silico analys ...[more]

PMID: 29540773

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Dataset Information

WSB-1 regulates the metastatic potential of hormone receptor negative breast cancer.

Background

Methods

Results

Conclusions

Publications

WSB-1 regulates the metastatic potential of hormone receptor negative breast cancer.

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