Non-melanoma (basal and squamous cell carcinoma) skin cancer is the most diagnosed cancer in Ireland. Its development is a complex multistep process of cellular and neoplastic transformation, its progression is reliant on local tissue invasion and distant metastasis. The acquisition of these latter capabilities is reliant on epithelial mesenchymal transition (EMT) at the invasive front within what is known as the tumour microenvironment (TME) In vitro, animal and molecular studies have revealed that tumour derived extracellular vesicles (EVs) under the regulation of hypoxia inducible factors (HIFs), have emerged as key regulators for cancer progression including the formation of a favourable microenvironment, recruitment of non-cancerous cells, cancer associated fibroblast (CAF) interactions and regulation of EMT. Essential to this is cytoskeletal remodelling which is known to be regulated by Rho GTPases but also reactive oxygen species (ROS). Interestingly, Rho GTPases, the actin cytoskeleton, HIFs and EVs release are all sensitive to redox regulation. Indeed ROS have also been extensively linked to the development and progression of many cancers. This knowledge must now be applied to patient samples.
This project aims to use a correlative light and electron microscopy (CLEM) combining the versatility of fluorescence microscopy with the resolution of electron microscopy, enabling analysis of larger volumes of tissues followed by the in-depth ultrastructural analysis of more precise areas of interest.
