ArticleCell death and differentiation2019
Targeting CDK7 increases the stability of Snail to promote the dissemination of colorectal cancer.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- Targeting CDK7 to overcome hypomethylating agent resistance in acute myeloid leukemia.Blood research · 2026Article
- ALKBH3-regulated mActa pharmaceutica Sinica. B · 2025Article
- Potential of Adora2b as an immunotherapeutic target for gastric cancer.Frontiers in immunology · 2025Review
- The role of circular RNA targeting IGF2BPs in cancer-a potential target for cancer therapy.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Discovery of bivalent small molecule degraders of cyclin-dependent kinase 7 (CDK7).European journal of medicinal chemistry · 2024Article
- Nanomedicine-induced programmed cell death in cancer therapy: mechanisms and perspectives.Cell death discovery · 2024Review
- Adenovirus vaccine targeting kinases induces potent antitumor immunity in solid tumors.Journal for immunotherapy of cancer · 2024Article
- CDK7 in breast cancer: mechanisms of action and therapeutic potential.Cell communication and signaling : CCS · 2024Review
- Targeting Myc-driven stress addiction in colorectal cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- The crosstalk between anoikis and epithelial-mesenchymal transition and their synergistic roles in predicting prognosis in colon adenocarcinoma.Frontiers in oncology · 2023Article
- Article
- Circular RNA circ-TNPO3 inhibits clear cell renal cell carcinoma metastasis by binding to IGF2BP2 and destabilizing SERPINH1 mRNA.Clinical and translational medicine · 2022Article
- Transcriptional inhibition of miR-486-3p by BCL6 upregulates Snail and induces epithelial-mesenchymal transition during radiation-induced pulmonary fibrosis.Respiratory research · 2022Article
- Control of Expression of Key Cell Cycle Enzymes Drives Cell Line-Specific Functions of CDK7 in Human PDAC Cells.International journal of molecular sciences · 2022Article
- Nucleophosmin 1 is a prognostic marker of gastrointestinal cancer and is associated with m6A and cuproptosis.Frontiers in pharmacology · 2022Article
- CDK7 is a prognostic biomarker for non-small cell lung cancer.Frontiers in oncology · 2022Article
- Super-enhancers in esophageal carcinoma: Transcriptional addictions and therapeutic strategies.Frontiers in oncology · 2022Review
- Identification of CDK7 Inhibitors from Natural Sources Using Pharmacoinformatics and Molecular Dynamics Simulations.Biomedicines · 2021Article
- Transcriptional CDK inhibitors, CYC065 and THZ1 promote Bim-dependent apoptosis in primary and recurrent GBM through cell cycle arrest and Mcl-1 downregulation.Cell death & disease · 2021Article
- 5'-tRF-GlyGCC: a tRNA-derived small RNA as a novel biomarker for colorectal cancer diagnosis.Genome medicine · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 related factors via qRT-PCR, results indicate THZ1 and si-CDK7 decrease the expression of protein kinase D1 (PKD1) in CRC cells. Down regulation of PKD1 mediates THZ1 up regulated Snail via dephosphorylation of Snail Ser 11 and prevention of proteasome mediated degradation. Clinical analysis confirms that CDK7 is significantly (p < 0.05) negatively correlated with the expression of mesenchymal markers including FN1, VIM, and MMP2. CRC patients whose tumors expressing less CDK7/SNAI1 or PKD1/SNAI1 showed significant (p < 0.05) poorer overall survival (OS) rate as compared with those with greater levels. Collectively, our data suggest that targeted inhibition of CDK7 can trigger the metastasis of CRC during cancer development via PKD1/Snail axis, which imposes great challenge that inhibition of CDK7 is a potential approach for cancer treatment.
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