ArticleOncogene2021
Plasmalemma vesicle-associated protein promotes angiogenesis in cholangiocarcinoma via the DKK1/CKAP4/PI3K signaling pathway.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 52 citations in OpenAlex.
- DKK1 in Cancer: A Bench-to-Bedside Review of Molecular Mechanisms and Clinical Applications.Cancers · 2026Review
- Single-cell epigenetic landscape, microenvironment interactions, and gene regulatory modules of non-functioning pituitary adenomas.Cell systems · 2026Article
- Oncofetal reprogramming in hepatocellular carcinoma: linking developmental programs to cancer vaccines and immunotherapy.Clinical and molecular hepatology · 2026Review
- 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
- Article
- Integrative multi-omics analysis reveals the role of tumor-associated endothelial cells and their signature in prognosis of intrahepatic cholangiocarcinoma.Journal of translational medicine · 2024Article
- Investigation into the role of H2-Ab1 in vascular remodeling in pulmonary arterial hypertension via Bioinformatics.BMC pulmonary medicine · 2024Article
- Immunohistochemical and Morphometric Assessment on the Biological Function and Vascular Endothelial Cells in the Initial Process of Cortical Porosity in Mice With PTH Administration.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024Article
- Article
- The scaffold of neutrophil extracellular traps promotes CCA progression and modulates angiogenesis via ITGAV/NFκB.Cell communication and signaling : CCS · 2024Article
- A network map of cytoskeleton-associated protein 4 (CKAP4) mediated signaling pathway in cancer.Journal of cell communication and signaling · 2023Article
- Understanding tumour endothelial cell heterogeneity and function from single-cell omics.Nature reviews. Cancer · 2023Review
- PLVAP protein expression correlated with microbial composition, clinicopathological features, and prognosis of patients with stomach adenocarcinoma.Journal of cancer research and clinical oncology · 2023Article
- Molecular signaling network and therapeutic developments in breast cancer brain metastasis.Advances in cancer biology - metastasis · 2023Article
- Formin-like 2 promotes angiogenesis and metastasis of colorectal cancer by regulating the EGFL6/CKAP4/ERK axis.Cancer science · 2023Article
- Identification of gene signatures related to hypoxia and angiogenesis in pancreatic cancer to aid immunotherapy and prognosis.Frontiers in oncology · 2023Article
- Mapping the tumor microenvironment in clear cell renal carcinoma by single-cell transcriptome analysis.Frontiers in genetics · 2023Article
- SMARCC2 mediates the regulation of DKK1 by the transcription factor EGR1 through chromatin remodeling to reduce the proliferative capacity of glioblastoma.Cell death & disease · 2022Article
- The Histone Demethylase Inhibitor GSK-J4 Is a Therapeutic Target for the Kidney Fibrosis of Diabetic Kidney Disease via DKK1 Modulation.International journal of molecular sciences · 2022Article
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
Cholangiocarcinoma (CCA) is aggressive and has poor clinical outcomes because of typically delayed diagnosis and a lack of effective non-surgical therapeutic options. Recent studies have shown that plasmalemma vesicle-associated protein (PLVAP) is related to angiogenesis in various tumors, and in vivo PLVAP targeting therapy has been proven effective against hepatocellular carcinoma and pancreatic cancer. The goal of this study was to determine the potential therapeutic utility of targeting PLVAP and thus angiogenesis in CCA and explore the underlying molecular mechanisms. We found that the PLVAP expression levels were significantly higher in CCA tissues when compared with matched adjacent non-tumor tissues obtained from a total of 90 CCA patients; higher expression levels of PLVAP were associated with shorter overall survival of patients. In addition, overexpression of PLVAP was associated with higher micro-vessel density in CCA tissues. In a PLVAP overexpressing CCA patient-derived xenograft model, a novel humanized anti-PLVAP antibody in combination with Gemcitabine plus Cisplatin was significantly inhibited tumor growth. Molecular analysis of CCA cells co-cultured with human umbilical vascular endothelial cells or human hepatic sinusoidal endothelial cells showed that Dickkopf-related protein 1 (DKK1) secreted by CCA cells activated the PI3K/Akt pathway after binding to its receptor, cytoskeleton-associated protein 4 (CKAP4), resulting in the upregulation of PLVAP. Thus, CCA cells increased the angiogenic potency of endothelial cells in a paracrine fashion. Consistently, patients bearing CKAP4 and PLVAP overexpressing tumors had a poor prognosis. In conclusion, the DKK1/CKAP4/PI3K/PLVAP pathway increases angiogenesis in CCA and is therefore a potential anti-angiogenic target.
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