ArticleCancer science2023
DKK1-CKAP4 signal axis promotes hepatocellular carcinoma aggressiveness.
Article in Cancer science, 2023. 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, 19 citations in OpenAlex.
- Article
- DKK1 Suppresses Hippo Signaling via PIPCancer communications (London, England) · 2026Article
- The Emerging Role of CKAP4 in GI Cancer: From Molecular Pathways to Clinical Applications.Current oncology (Toronto, Ont.) · 2025Review
- Cytoskeleton-associated protein 4: a double-edged sword in cell growth and aging.Biogerontology · 2025Review
- Targeting unique ligand binding domain structural features downregulates DKK1 in Y537S ESR1 mutant breast cancer cells.Breast cancer research : BCR · 2025Article
- DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target.Diagnostics (Basel, Switzerland) · 2025Review
- Newly developed humanized anti-CKAP4 antibody suppresses pancreatic cancer growth by inhibiting DKK1-CKAP4 signaling.Cancer science · 2024Article
- DKK1 as a chemoresistant protein modulates oxaliplatin responses in colorectal cancer.Oncogenesis · 2024Article
- Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537SResearch square · 2024Article
- The Role of Serum Dickkopf1 and CKAP4 Levels in Diagnosing Colorectal Cancer and Measuring the Disease Severity: A Prospective Study.Medicina (Kaunas, Lithuania) · 2024Article
- Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537SbioRxiv : the preprint server for biology · 2024Article
- The Combined Use of Dickkopf-1 and Soluble Axl Improves Hepatocellular Carcinoma Diagnostic Efficacy in Hepatitis C Patients.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Identification of tumor heterogeneity associated with KRAS/TP53 co-mutation status in lung adenocarcinoma based on single-cell RNA sequencing.American journal of cancer research · 2024Article
- Article
- DKK1-CKAP4 signal axis promotes hepatocellular carcinoma aggressiveness.Cancer science · 2023Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent malignant liver neoplasm. Despite the advances in diagnosis and treatment, the prognosis of HCC patients remains poor. Cytoskeleton-associated membrane protein 4 (CKAP4) is a receptor of the glycosylated secretory protein Dickkopf-1 (DKK1), and the DKK1-CKAP4 axis is activated in pancreatic, lung, and esophageal cancer cells. Expression of DKK1 and CKAP4 has been examined in HCC in independent studies that yielded contradictory results. In this study, the relationship between the DKK1-CKAP4 axis and HCC was comprehensively examined. In 412 HCC cases, patients whose tumors were positive for both DKK1 and CKAP4 had a poor prognosis compared to those who were positive for only one of these markers or negative for both. Deletion of either DKK1 or CKAP4 inhibited HCC cell growth. In contrast to WT DKK1, DKK1 lacking the CKAP4 binding region did not rescue the phenotypes caused by DKK1 depletion, suggesting that binding of DKK1 to CKAP4 is required for HCC cell proliferation. Anti-CKAP4 Ab inhibited HCC growth, and its antitumor effect was clearly enhanced when combined with lenvatinib, a multikinase inhibitor. These results indicate that simultaneous expression of DKK1 and CKAP4 is involved in the aggressiveness of HCC, and that the combination of anti-CKAP4 Ab and other therapeutics including lenvatinib could represent a promising strategy for treating advanced HCC.
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Registered trials
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