Background: Colorectal cancer (CRC) is the second most common cause of cancer-related mortality in the UK due to high rates of metastasis and therapy relapse. Important molecular drivers of these processes are intra-tumour heterogeneity and phenotypic plasticity, where diverse subclones exist in the same tumour and they can adopt different transcriptional states without acquiring underlying genetic changes. Recently, we described non-canonical cell states, such as hybrid-EMT, squamous and neuroendocrine in mouse models. These states have also been observed in patient samples associated with poorer prognosis. We aim to characterise non-canonical states at a single-cell and spatial level in murine organoid models of advanced CRC and elucidate their role in advanced disease. In Apcfl/fl, KrasG12D, Trp53fl/fl (AKP) organoids, knockout of the chromatin remodelling enzyme Atrx led to increased metastasis and emergence of a hybrid-EMT transcriptional phenotype characterised by loss of colonic epithelial genes.