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Characterisation of the role of the adhesion protein tensin 3 in breast cancer progression


Department of Biomedical Science

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Dr E Rainero Applications accepted all year round Self-Funded PhD Students Only

About the Project

Breast cancer arises from the transformation of mammary epithelial cells. In the healthy tissue, these grow as a single monolayer of cells delimiting an internal hollow lumen 2. Key to the ability of these cells to polarise is the interaction with the surrounding basement membrane, a specialised type of extracellular matrix (ECM). During carcinoma progression, cell proliferation leads to filling of the lumen and formation of ductal carcinoma in situ (DCIS). Acquisition of invasive ability then allows cancer cells to break through the basement membrane and disseminate in the surrounding tissues, resulting in invasive ductal carcinoma (IDC). The crosstalk between cancer cells and the microenvironment has been identified as one of the areas where more research is needed. The ECM is a complex network of secreted proteins which not only provides tissue support, but is also involved in the control of several cell functions, including migration and oncogenic transformation3. The tumour microenvironment has a pivotal role in modulating cancer initiation, progression and metastasis, while cancer cells in turn modify the composition and properties of the ECM, demonstrating a bi-directional interaction between tumour and the ECM.
We have identified tensin as a crucial regulator of the trafficking of cell adhesion receptors of the integrin family, which promotes ECM endocytosis. We hypothesise that the adhesion protein tensin 3 (TNS3) is a key mediator of the transition from DCIS to IDC, through the regulation of ECM dynamics. This is particularly important considering the fact that 20-50% of DCIS lesions progress to IDC, but to date reliable indicators of invasive progression are missing 5. Importantly, despite the clear indication that ECM remodelling accompanies DCIS to IDC transition, the underlying molecular mechanisms have not been investigated 5. The findings of this study will significantly progress our understanding of breast cancer progression, guiding and contributing to the development of the field of cell-ECM adhesion.
Using advanced imaging techniques and 3D cell culture systems, this project will:
- Characterise the role of TNS3 in controlling ECM uptake and breast cancer cell invasive migration
- Elucidate how TNS3 controls ECM organisation and invasive carcinoma progression
- Define whether TNS3 expression correlates with breast cancer progression in humans
The outcomes of this project will determine whether targeting TNS3-dependent integrin trafficking may represent a novel strategy to limit invasive breast cancer.

Science Graduate School
As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit www.sheffield.ac.uk/sgs to learn more.

Funding Notes

First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University's application form using the following link: http://www.sheffield.ac.uk/postgraduate/research/apply/applying

All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information.
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