Integrated multi-omics analysis reveals that tumour cell-intrinsic DCLK1 is associated with an angiogenic tumour microenvironment in cholangiocarcinoma via NF-κB/CXCL5
- 1Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020 China
Abstract
Purpose: Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis and complex tumour microenvironment. We previously demonstrated that doublecortin-like kinase 1 (DCLK1) is associated with epithelial–mesenchymal transition (EMT) in CCA; however, its biological functions and clinical relevance remain unclear. Herein, we elucidated the role of DCLK1 in CCA progression, focusing on its effects on angiogenesis, and evaluated its potential as a prognostic marker.
Methods: We analysed bulk and single-cell RNA sequencing data to characterise DCLK1 expression and function in CCA. Functional validation was performed using conditioned medium from DCLK1-modified CCA cells, as well as endothelial tube formation, migration, and invasion assays. Tumour vascular density was assessed using a xenograft model. We used a human angiogenesis-related antibody array, western blotting, quantitative real-time PCR, and nuclear translocation assays to examine CXCL5 expression and NF-κB pathway activity.
Result: We found that DCLK1 was upregulated in CCA and correlated with advanced disease and poor survival. DCLK1⁺ malignant cells displayed pro-angiogenic features and increased paracrine interaction with endothelial cells. Conditioned medium from DCLK1-overexpressing tumour cells enhanced endothelial tube formation, migration, and invasion, whereas DCLK1 knockout reversed these effects. DCLK1-expressing tumours showed increased vascular density in vivo. Mechanistically, an angiogenesis antibody array and western blotting demonstrated that DCLK1 activated the NF-κB pathway to upregulate CXCL5 expression. Pharmacological inhibition of NF-κB or neutralization of CXCL5 significantly attenuated DCLK1-related pro-angiogenic responses in vitro.
Conclusion: DCLK1 activated the NF-κB pathway to upregulate CXCL5 secretion; inhibiting NF-κB or CXCL5 reduced DCLK1-related pro-angiogenic capacity.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00432-026-06568-9.
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BibTeX
@article{kong2026integrated,
title = {{Integrated multi-omics analysis reveals that tumour cell-intrinsic DCLK1 is associated with an angiogenic tumour microenvironment in cholangiocarcinoma via NF-κB/CXCL5}},
author = {Ziqing Kong and Rui Yan and Ziwei Liang and Guangyu An and Yang Ge},
journal = {Journal of Cancer Research and Clinical Oncology},
year = {2026},
month = jul,
doi = {10.1007/s00432-026-06568-9},
url = {https://doi.org/10.1007/s00432-026-06568-9},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Integrated multi-omics analysis reveals that tumour cell-intrinsic DCLK1 is associated with an angiogenic tumour microenvironment in cholangiocarcinoma via NF-κB/CXCL5
AU - Ziqing Kong
AU - Rui Yan
AU - Ziwei Liang
AU - Guangyu An
AU - Yang Ge
PY - 2026
DA - 2026/07/29
JO - Journal of Cancer Research and Clinical Oncology
DO - 10.1007/s00432-026-06568-9
UR - https://doi.org/10.1007/s00432-026-06568-9
AB - Purpose: Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis and complex tumour microenvironment. We previously demonstrated that doublecortin-like kinase 1 (DCLK1) is associated with epithelial–mesenchymal transition (EMT) in CCA; however, its biological functions and clinical relevance remain unclear. Herein, we elucidated the role of DCLK1 in CCA progression, focusing on its effects on angiogenesis, and evaluated its potential as a prognostic marker. Methods: We analysed bulk and single-cell RNA sequencing data to characterise DCLK1 expression and function in CCA. Functional validation was performed using conditioned medium from DCLK1-modified CCA cells, as well as endothelial tube formation, migration, and invasion assays. Tumour vascular density was assessed using a xenograft model. We used a human angiogenesis-related antibody array, western blotting, quantitative real-time PCR, and nuclear translocation assays to examine CXCL5 expression and NF-κB pathway activity. Result: We found that DCLK1 was upregulated in CCA and correlated with advanced disease and poor survival. DCLK1⁺ malignant cells displayed pro-angiogenic features and increased paracrine interaction with endothelial cells. Conditioned medium from DCLK1-overexpressing tumour cells enhanced endothelial tube formation, migration, and invasion, whereas DCLK1 knockout reversed these effects. DCLK1-expressing tumours showed increased vascular density in vivo. Mechanistically, an angiogenesis antibody array and western blotting demonstrated that DCLK1 activated the NF-κB pathway to upregulate CXCL5 expression. Pharmacological inhibition of NF-κB or neutralization of CXCL5 significantly attenuated DCLK1-related pro-angiogenic responses in vitro. Conclusion: DCLK1 activated the NF-κB pathway to upregulate CXCL5 secretion; inhibiting NF-κB or CXCL5 reduced DCLK1-related pro-angiogenic capacity. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00432-026-06568-9.
SN - 0171-5216
SN - 1432-1335
ER -