Traditionally, malignancy has been defined as a cell-autonomous phenomenon that is acquired through clonal selection of neoplastic cells that have gained driver mutations conferring invasive and/or metastatic properties. However, driver mutations responsible for metastasis have yet to be identified. On the other hand, the importance of the tumour microenvironment in malignancy progression is recognized, despite its underlying developmental process remaining unknown. We hypothesize that the gain of non-cell autonomous ability within somatic epithelial cells, such as inflammatory secretions, is the onset of malignancy as it initiates interactions with surrounding cell populations, particularly tissue residential macrophages (TRMs), ultimately leading to metastasis. Recent studies have demonstrated that chromosomal instability falsely activates the cGAS-STING cascade, an innate viral DNA sensing system. Chronic low-grade activation of this pathway has been shown to contribute towards the development of metastatic phenotypes. We envision that false activation of innate viral sensing systems triggers interaction with neighbouring cells, particularly TRMs, leading to the development of a malignancy inducing tumour microenvironment.  To address this, we are generating a conditional constitutively active allele of STING, an adapter protein within the cytosolic DNA-Sensing cGAS-STING cascade, upstream of the Type I IFN response. We will test if the activation of this allele within the context of a benign tumour is sufficient to drive malignancy progression.