biostudies-literatureUnknown26(8)Zhou YTargeted inhibition of cyclin-dependent kinase 7 (CDK7) via its covalent inhibitor THZ1 can suppress the growth of various cancers, while its roles on colorectal cancer (CRC) remain obscure. Here we report that the expression of CDK7 is upregulated in CRC cells and tissues. THZ1 exhibits high potency and selectivity against CRC cells both in vitro and in vivo via induction of cell apoptosis rather than cell cycle disruption. Intriguingly, THZ1 treatment increases the ability of epithelial mesenchymal transition (EMT) and in vivo metastasis to liver of CRC cells. Mechanistical studies reveal that THZ1 increases the expression of Snail, while not other EMT-transcription factors, via enhancing its protein stability rather than mRNA expression or translation. By screening Snail stability relatCell death and differentiation1442-1452https://www.ebi.ac.uk/biostudies/studies/S-EPMC6748077biostudies-literatureTargeting CDK7 increases the stability of Snail to promote the dissemination of colorectal cancer.PMC6748077Lu LAn PLi JChen ZJiang GChen LDu JWang HZhou YfalseTargeting CDK7 increases the stability of Snail to promote the dissemination of colorectal cancer.Targeted inhibition of cyclin-dependent kinase 7 (CDK7) via its covalent inhibitor THZ1 can suppress the growth of various cancers, while its roles on colorectal cancer (CRC) remain obscure. Here we report that the expression of CDK7 is upregulated in CRC cells and tissues. THZ1 exhibits high potency and selectivity against CRC cells both in vitro and in vivo via induction of cell apoptosis rather than cell cycle disruption. Intriguingly, THZ1 treatment increases the ability of epithelial mesenchymal transition (EMT) and in vivo metastasis to liver of CRC cells. Mechanistical studies reveal that THZ1 increases the expression of Snail, while not other EMT-transcription factors, via enhancing its protein stability rather than mRNA expression or translation. By screening Snail stability relat2019-01-01T00:00:00Z2019 Aug2025-04-19T04:29:12.129Z2025-04-19T04:29:12.129ZS-EPMC67480773045198910.1038/s41418-018-0222-4