PhD Research Project: Investigating the role of the adhesion protein Tensin 3 in breast cancer inva
The extracellular matrix (ECM) is a complex network of secreted proteins that, besides providing the scaffolding onto which tissue and organs are organised, is involved in the regulation of a variety of cell function, including survival, growth, migration and differentiation. Moreover, the interaction with the ECM has an important role in controlling tumour formation and metastasis in several cancer types, including breast cancer. Cells interact with the ECM through plasma membrane receptors, including the integrin family, which have a key role in controlling cancer cell invasion and migration. Integrins are not only found at the cell surface, but can be internalised and either be targeted for lysosomal degradation or transported back to the plasma membrane. Interestingly, the way in which integrins are trafficked intracellularly dictates how they control cell migration. My lab focuses on cell-ECM interaction from a novel and exciting angle, analysing the role of the internalisation of ECM components in promoting cancer invasiveness.
My data indicate that invasive breast cancer cells strongly up-regulate ECM uptake, compared to normal mammary epithelial cells, and the integrin-binding protein tensin-3 is required for this. Interestingly, high expression of tensin-3 correlates with poor prognosis in a cohort of breast cancer patients, supporting its role in cancer progression.
The aim of this project is the characterisation of the molecular mechanisms through which tensin-3 controls ECM internalisation and how this impinges on cancer cell invasion, analysing in particular: (1) whether tensin-3 controls ECM endocytosis through the regulation of integrin function; (2) how tensin-3 controls ECM organisation and turnover in 3D environment; (3) what is the role of tensin-3 in cancer cell migration and invasion, in both 2D and 3D settings. To mimic the physiological environment, fibroblast-generated cell-derived matrices and 3D culture systems will be used, coupled with confocal and time-lapse video microscopy.
The outcome of this project will shed new light on the role of ECM trafficking in cancer and will determine whether tensin-3 may represent a target for the development of novel anti-cancer therapeutic strategies.
Applications from self-funded students or students with secured funding are also welcome.
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD Studentship, you must complete the University's application form using the following link: http://www.sheffield.ac.uk/bms/prospective_pg/how_to_apply
*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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