Website The University of Sheffield
Details
Breast and pancreatic tumours are characterised by excessive deposition of extracellular matrix (ECM) components, resulting in extensive fibrosis, which in turn promotes tumour progression and metastasis. Our lab has recently demonstrated that cancer cells, but not normal epithelial cells, are able to internalise ECM components, digest them in the lysosomes and use them as energy sources. Importantly, this process was required to promote cell growth and cell migration in both breast and pancreatic cancer cells. Therefore, identifying regulators of this process might lead to the development of novel anti-cancer therapies.
Preliminary data indicate that the degradation of ECM by cathepsin proteases is required for ECM internalisation. The overall aim of this project is to elucidate the role of cathepsin in promoting cancer growth and migration, and define the molecular mechanisms behind it. In particular, this project is composed of 3 objectives:
– Objective 1: we will characterise the expression of different members of the cathepsin family and elucidation of the role of specific cathepsins in controlling ECM uptake
– Objective 2: as cathepsins are lysosomal protein that can be secreted, here we will define how cathepsin secretion works and whether this is stimulated during tumour progression
– Objective 3: we will define the role of cathepsin in controlling cancer cell growth and invasion, using a variety of 2D and 3D cancer models.
Together, this project will determine whether specific cathepsins might represent novel targets to prevent tumour growth and migration.
Please apply for this project using this link: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying
Funding Notes
Self or externally funded students only.
References
Nazemi et al., PLOS Biology 2024
Martinez et al., PLOS Biology 2024
https://www.sheffield.ac.uk/biosciences/people/academic-staff/elena-rainero
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