ArticleOncogene2020
KNK437 restricts the growth and metastasis of colorectal cancer via targeting DNAJA1/CDC45 axis.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Prognostic role of HSPs in human colorectal cancer: a systematic review and meta-analysis.BMC cancer · 2026Pooled it
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Mechanism-based prediction of drug synergy via network controllability analysis of therapeutic pathways in intractable diseases.iScience · 2026Article
- Identification of a novel and a recurrentFrontiers in genetics · 2026Article
- Enhancement of 5-fluorouracil efficacy in colorectal cancer cells through thymidylate synthase inhibition by sodium propionate.In vitro cellular & developmental biology. Animal · 2025Article
- DNAJA: emerging targets for anti-tumor therapy.Future oncology (London, England) · 2025Review
- Construction and validation of a regulatory T cells-based classification of renal cell carcinoma: an integrated bioinformatic analysis and clinical cohort study.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Heat Shock Protein Family A Member 1A Attenuates Apoptosis and Oxidative Stress via ERK/JNK Pathway in Hyperplastic Prostate.MedComm · 2025Article
- Itaconate Ameliorates Experimental Autoimmune Uveitis by Modulating Teff/Treg Cell Imbalance Via the DNAJA1/CDC45 Axis.Investigative ophthalmology & visual science · 2024Article
- GRAIL1 Stabilizes Misfolded Mutant p53 through a Ubiquitin Ligase-Independent, Chaperone Regulatory Function.Molecular cancer research : MCR · 2024Article
- Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.Journal of hematology & oncology · 2024Review
- Tert-expressing cells contribute to salivary gland homeostasis and tissue regeneration after radiation therapy.Genes & development · 2024Article
- The role of HSP40 in cancer: Recent advances.Histology and histopathology · 2024Review
- Integration of single-cell sequencing and bulk RNA-seq to identify and develop a prognostic signature related to colorectal cancer stem cells.Scientific reports · 2024Article
- Unwinding Helicase MCM Functionality for Diagnosis and Therapeutics of Replication Abnormalities Associated with Cancer: A Review.Molecular diagnosis & therapy · 2024Review
- Review
- CDC45 promotes the stemness and metastasis in lung adenocarcinoma by affecting the cell cycle.Journal of translational medicine · 2024Article
- Upregulation of lnc-FOXD2-AS1, CDC45, and CDK1 in patients with primary non-M3 AML is associated with a worse prognosis.Blood research · 2024Article
- HSF1 at the crossroads of chemoresistance: from current insights to future horizons in cell death mechanisms.Frontiers in cell and developmental biology · 2024Review
- Inhibition of Hsp110-STAT3 interaction in endothelial cells alleviates vascular remodeling in hypoxic pulmonary arterial Hypertension model.Respiratory research · 2023Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As an inhibitor of heat shock proteins (HSPs), KNK437 has been reported to play an anti-tumor role in several cancers. But its therapeutic effect and mechanisms in colorectal cancer (CRC) remain unclear. Here, KNK437 sharply inhibited the level of DnaJ heat shock protein family (Hsp40) member A1 (DNAJA1), followed by DNAJB1, but had little effect on the levels of HSP27, HSP105, HSP90, and HSP70 in CRC cells. DNAJA1 promoted CRC cell proliferation in vitro and tumor growth and metastasis in vivo. Mechanistically, DNAJA1 was activated by E2F transcription factor 1 (E2F1) and then promoted cell cycle by stabilizing cell division cycle protein 45 (CDC45), which could be reversed by KNK437. DNAJA1 was significantly upregulated in CRC tissues and positively correlated with serosa invasion, lymph node metastasis. High level of DNAJA1 predicted poor prognosis for CRC patients. Its expression was highly linked with E2F1 and CDC45 in CRC tissues. More importantly, KNK437 significantly suppressed the growth of DNAJA1 expressing tumor in vivo. The combined treatment of KNK437 with 5-FU/L-OHP chemotherapy reduced liver metastasis of CRC. These data reveal a novel mechanism of KNK437 in anti-tumor therapy of CRC and provides a newly therapeutic strategy with potential translation to the CRC patients.
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