Combining active rasG12V expression with RNA interference (RNAi) knockdown of tumour suppressors apc, p53, smad4, and/or PTEN in Drosophila recapitulated key colorectal cancer (CRC) pathologies, including cell proliferation, epithelial-mesenchymal transition (EMT), and distant metastasis. Here, SMAD4 is linked to colorectal cancer.