ArticlePloS one2017
The prognostic significance of DAPK1 in bladder cancer.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- DAPK1 identified as a novel biomarker for colorectal cancer liver metastasis.Cancer cell international · 2025Article
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- Tripartite motif-containing 9 promoted proliferation and migration of bladder cancer cells through CEACAM6-Smad2/3 axis.Journal of cell communication and signaling · 2023Article
- Death-associated protein kinase 1 phosphorylates MDM2 and inhibits its protein stability and function.Archives of pharmacal research · 2023Article
- Reprogramming of palmitic acid induced by dephosphorylation of ACOX1 promotes β-catenin palmitoylation to drive colorectal cancer progression.Cell discovery · 2023Article
- Genome-wide RNA-sequencing dataset revealsJournal of Cancer · 2023Article
- Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features.Open life sciences · 2023Article
- Article
- Regulatory Non-coding RNAs for Death Associated Protein Kinase Family.Frontiers in molecular biosciences · 2021Review
- Regulation of the Expression of DAPK1 by SUMO Pathway.Biomolecules · 2019Article
- TMED2 as a marker of prognosis in breast cancer [Letter].Cancer management and research · 2019Article
- Marked Global DNA Hypomethylation Is Associated with Constitutive PD-L1 Expression in Melanoma.iScience · 2018Article
- Concurrent regulation of LKB1 and CaMKK2 in the activation of AMPK in castrate-resistant prostate cancer by a well-defined polyherbal mixture with anticancer properties.BMC complementary and alternative medicine · 2018Article
- Preliminary Evaluation of the Diagnostic Usefulness of Uroplakin 2 with an Assessment of the Antioxidant Potential of Patients with Bladder Cancer.BioMed research international · 2018Article
- Emerging Biomarkers in Bladder Cancer Identified by Network Analysis of Transcriptomic Data.Frontiers in oncology · 2018Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bladder cancer is one of the leading causes of cancer-related death in men, however, there was only limited effective treatment for invasive bladder cancer. DAPK1 has been shown to play important role in apoptosis and autophagy to suppress cancer progression. Previous results have shown that DAPK1 promoter was hypermethylated in the majority of bladder cancer specimens, however, the prognostic significance of DAPK1 in bladder cancer has yet to be demonstrated. In the present study, we found that DAPK1 expression was negatively associated with tumor stage and a low level expression of DAPK1 in bladder cancer specimens were associated with shorter survival in bladder cancer patients in 3 independent bladder cancer datasets (n = 462). Further investigation showed that FGFR3 knockdown resulted in downregulation of DAPK1 in bladder cancer cell line, suggesting that FGFR3 may be an upstream factor of DAPK1. Further analysis of the 3 independent bladder cancer datasets have identified ACOX1, UPK2, TRAK1, PLEKHG6 and MT1X genes had their expression significantly correlated with that of DAPK1. Knockdown of DAPK1 in bladder cancer T24 cells resulted in downregulation of ACOX1, UPK2 and TRAK1. Interestingly, TRAK1, by itself, was a favorable prognostic marker in the 3 independent bladder cancer datasets. Importantly, by using connectivity mapping with DAPK1-associated gene signature, we found that vemurafenib and trametinib could possibly reverse DAPK1-associated gene signature, suggesting that inhibition of Raf/MEK pathway may be a potential therapeutic approach for bladder cancer. Indeed, treatment of vemurafenib in T24 bladder cancer cells resulted in upregulation of DAPK1 confirming our connectivity mapping, while knockdown of DAPK1 resulted in reduced sensitivity towards inhibition of Braf signaling by vemurafenib. Together, our results suggest that DAPK1 is an important prognostic marker and therapeutic target for bladder cancer and have identified possible therapeutic agents for future testing in bladder cancer models with low DAPK1 expression.
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