Trial reportThe Journal of clinical investigation2012
CHK1 targets spleen tyrosine kinase (L) for proteolysis in hepatocellular carcinoma.
Trial report in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- Potential role of microRNA‑223‑3p in the tumorigenesis of hepatocellular carcinoma: A comprehensive study based on data mining and bioinformatics.Molecular medicine reports · 2018Pooled it
- Targeting SYK to alleviate MDSC-driven immunosuppression and augment anti-PD1 efficacy.Science China. Life sciences · 2026Article
- Polyporusterone E, a Key Component ofInternational journal of molecular sciences · 2026Article
- Multiomics integration prioritizes potential drug targets for lung cancer.Discover oncology · 2026Article
- An HDAC4-specific PROTAC degrader achieves radiation sensitization by enhancing ferroptosis in lung cancer.Nature communications · 2026Article
- CRISPR/Cas9 library screening uncovered CCT2 as a critical driver of acquired resistance to EGFR-targeted therapy by stabilizing TMX1 in non-small cell lung cancer.Cell death and differentiation · 2026Article
- IsoProDB: an integrated map of human protein isoforms for accelerated research.Database : the journal of biological databases and curation · 2026Article
- CHK1 inhibition overcomes gemcitabine resistance in non-small cell lung cancer cell A549.Molecular & cellular oncology · 2025Article
- Expression of variant isoforms of the tyrosine kinase SYK differentially regulates cervical cancer progression through PI3K/AKT pathway.Scientific reports · 2024Article
- Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.Molecular cancer · 2024Article
- Novel Amidine Derivative K1586 Sensitizes Colorectal Cancer Cells to Ionizing Radiation by Inducing Chk1 Instability.International journal of molecular sciences · 2024Article
- Triple-Negative Breast Cancer and Emerging Therapeutic Strategies: ATR and CHK1/2 as Promising Targets.Cancers · 2024Review
- SPRTN is involved in hepatocellular carcinoma development through the ER stress response.Cancer gene therapy · 2024Article
- Cathepsin K inhibition induces Raptor destabilization and mitochondrial dysfunction via Syk/SHP2/Src/OTUB1 axis-mediated signaling.Cell death & disease · 2023Article
- Article
- Dopamine receptor D3 is related to prognosis in human hepatocellular carcinoma and inhibits tumor growth.BMC cancer · 2022Article
- The spleen tyrosine kinase (SYK): A crucial therapeutic target for diverse liver diseases.Heliyon · 2022Review
- Checkpoint Kinase 1 (CHK1) Functions as Both a Diagnostic Marker and a Regulator of Epithelial-to-Mesenchymal Transition (EMT) in Triple-Negative Breast Cancer.Current issues in molecular biology · 2022Article
- Transcriptional factor III A promotes colorectal cancer progression by upregulating cystatin A.World journal of gastrointestinal oncology · 2022Article
- The SKP2-p27 axis defines susceptibility to cell death upon CHK1 inhibition.Molecular oncology · 2022Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies resistant to current chemotherapies or radiotherapies, which makes it urgent to identify new therapeutic targets for HCC. In this study, we found that checkpoint kinase 1 (CHK1) was frequently overexpressed and correlated with poor clinical outcome in patients with HCC. We further showed that the CHK1 inhibitor GÖ6976 was capable of sensitizing HCC cells to cisplatin, indicating that CHK1 may have oncogenic function in HCC. We found that CHK1 phosphorylated the tumor suppressor spleen tyrosine kinase (L) (SYK[L]) and identified the phosphorylation site at Ser295. Furthermore, CHK1 phosphorylation of SYK(L) promoted its subsequent proteasomal degradation. Expression of a nonphosphorylated mutant of SYK(L) was more efficient at suppressing proliferation, colony formation, mobility, and tumor growth in HCC lines. Importantly, a strong inverse correlation between the expression levels of CHK1 and SYK(L) was observed in patients with HCC. Collectively, our data demonstrate that SYK(L) is a substrate of CHK1 in tumor cells and suggest that targeting the CHK1/SYK(L) pathway may be a promising strategy for treating HCC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.