Objective:
To form metastasis, tumour cells need to leave the primary tumour, reach the blood flow, colonize distant tissues, and establish secondary tumours. Using state of the art lineage tracing in mouse models of skin SCCs presenting spontaneous lung and lymph node metastasis and epithelial to mesenchymal transition (EMT), we will assess the importance of EMT and mesenchymal to epithelial transition (MET) in regulating the development of metastasis. Using single cell RNA and ATAC sequencing, we will unravel the tumour states present in the primary tumours, circulating tumour cells (CTCs) and at the metastatic sites. We will define the functional role of these different tumour states and the molecular mechanisms regulating their transition using genetic gain and loss of function and pharmacological inhibition of the pathways uncovered by these analyses. This study will provide key insights into the molecular mechanisms that regulate tumour transition states controlling metastasis.
