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Here we demonstrate that inhibition of CDK4\/6 blocks breast tumour metastasis in the triple-negative breast cancer model, without affecting tumour growth. Mechanistically, we identify a deubiquitinase, DUB3, as a target of CDK4\/6; CDK4\/6-mediated activation of DUB3 is essential to deubiquitinate and stabilize SNAIL1, a key factor promoting epithelial\u2013mesenchymal transition and breast cancer metastasis. 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