Tumour dormancy is characterized by a reversible cell cycle arrest of tumour cells and is thought to be the cause of metastasis relapse years after remission. The mechanisms that regulate tumour dormancy are poorly understood. We will use a model of skin squamous cell carcinoma, in which fluorescently labelled tumour cells (TCs) spontaneously form metastasis in the lung, to decipher the mechanisms that control metastasis dormancy. In this model, we have found that isolated quiescent TCs could be identified. To uncover the mechanisms that control metastasis dormancy, we will micro-dissect overt metastases, FACS isolate fluorescently quiescent and proliferative TCs, and perform single cell RNA seq to identify the gene signature of dormant and proliferative metastatic cells. We will then use pharmacological approaches to assess the function of candidate signalling pathways that are likely to mediate dormancy and the function of these genes or pathways in the regulation of lung metastasis proliferation will be assessed. This study will be important to uncover new regulators of metastasis dormancy with important implications for cancer therapy.