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Investigating the role of WSB-1 in breast cancer

Poujade, Flore-Anne

Authors

Flore-Anne Poujade



Contributors

Isabel M. Pires
Supervisor

John (Professor of tumour immunology) Greenman
Supervisor

Abstract

Breast cancer is the second most represented cancer type worldwide and will affect 1 in 8 women in the UK. Overall patient survival can reach 90% when the disease is diagnosed early but rapidly drops as the tumour progresses and metastasises. The steps required for tumour formation are known but numerous factors are involved and the specific mechanisms controlling this phenomenon are still poorly understood. WSB-1 is a hypoxia-responsive E3 ubiquitin ligase which was found to be upregulated in metastatic tissues, compared to normal or non invasive tissues. In addition, studies demonstrated that WSB-1 was involved in pancreatic cancer, neuroblastoma, and osteosarcoma progression. However, its role in breast cancer has not been particularly studied.

The objective of this thesis is to study the role of WSB-1 in breast cancer. Initially, level of WSB1 in patients' tumour cDNA samples was evaluated according to known clinical and biological variables. Impact of high WSB1 levels on patients' distant metastasis-free survival, relapse-free survival and overall survival was also investigated. Then, the effect of WSB-1 knockdown on protein levels of epithelial to mesenchymal transition markers, as well as several matrix metalloproteinases (MMP) transcript and protein levels, and activity was examined. Consequence of these modifications on cell motility (migration, invasion) was studied, using single cells, cellular monolayers and spheroids. Finally, affinity purification followed by mass spectrometry was used to identify novel WSB-1 partners.

Overall, in MDA-MB-231 cells, WSB-1 appeared to drive metastasis formation by upregulating MMPs expression and activity, promoting EMT and inducing invasiveness. WSB-1 had a more conflicting effect in MCF7 cells. In fact, WSB-1 effect appeared to be depending on the ER- and ER+ status.

Together, these results validated WSB-1 as an important player in breast cancer development, particularly in metastasis formation.

Citation

Poujade, F. (2016). Investigating the role of WSB-1 in breast cancer. (Thesis). University of Hull. Retrieved from https://hull-repository.worktribe.com/output/4219511

Thesis Type Thesis
Deposit Date Aug 23, 2017
Publicly Available Date Feb 23, 2023
Keywords Biological sciences
Public URL https://hull-repository.worktribe.com/output/4219511
Additional Information School of Biological, Biomedical and Environmental Sciences, The University of Hull
Award Date Mar 1, 2016

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Thesis (7.3 Mb)
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Copyright Statement
© 2016 Poujade, Flore-Anne. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.


Table B1 cDNA microarray.xlsx (61 Kb)
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Copyright Statement
© 2016 Poujade, Flore-Anne. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.


Table B2 A_vs_B.xlsx (5.2 Mb)
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Copyright Statement
© 2016 Poujade, Flore-Anne. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.


Table B3 A_vs_C.xlsx (4.8 Mb)
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Copyright Statement
© 2016 Poujade, Flore-Anne. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.


Table B4 A_vs_D.xlsx (5.2 Mb)
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Copyright Statement
© 2016 Poujade, Flore-Anne. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.


Table B5 B_vs_C.xlsx (5.2 Mb)
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Copyright Statement
© 2016 Poujade, Flore-Anne. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.


Table B6 B_vs_D.xlsx (3.4 Mb)
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Copyright Statement
© 2016 Poujade, Flore-Anne. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.


Table B7 C_vs_D.xlsx (3.6 Mb)
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Copyright Statement
© 2016 Poujade, Flore-Anne. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.


Table B8 LC-MS raw data.xlsx (202 Kb)
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Copyright Statement
© 2016 Poujade, Flore-Anne. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.




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