Elevation of CXCL1 indicates poor prognosis and radioresistance by inducing mesenchymal transition in glioblastoma
Open Access
- 18 March 2020
- journal article
- research article
- Published by Wiley in CNS Neuroscience & Therapeutics
- Vol. 26 (4), 475-485
- https://doi.org/10.1111/cns.13297
Abstract
Introduction Glioblastoma (GBM) is identified as a lethal malignant tumor derived from the nervous system. Despite the standard clinical strategy including maximum surgical resection, temozolomide (TMZ) chemotherapy, and radiotherapy, the median survival of GBM patients remains <15 months. Accumulating evidence indicates that rapid‐acquired radioresistance is one of the most common reasons for GBM recurrence. Therefore, developing novel therapeutic targets for radioresistant GBM could yield long‐term cures. Aims To investigate the functional role of CXCL1 in the acquired radioresistance and identify the molecular pathway correlated to CXCL1. Results In this study, we identified that CXCL1 is highly expressed in GBM and the elevation of CXCL1 is involved in radioresistance and poor prognosis in GBM patients. Additionally, silencing CXCL1 attenuated the proliferation and radioresistance of GBM cells. Furthermore, we demonstrated that CXCL1‐overexpression induced radioresistance through mesenchymal transition of GBM via the activation of nuclear factor‐kappa B (NF‐κB) signaling. Conclusion CXCL1 was highly enriched in GBM and positively correlated with poor prognosis in GBM patients. Additionally, elevated CXCL1 induced radioresistance in GBM through regulation of NF‐κB signaling by promoting mesenchymal transition in GBM.Keywords
Funding Information
- The National Natural Science Foundation of China (81802502)
- Natural Science Basic Research Plan in Shaanxi Province of China (2019JQ-958)
- The First Affiliated hospital of Xi'an Jiaotong University and the Fundamental Research Funds of Xi'an Jiaotong University (1191329177)
This publication has 54 references indexed in Scilit:
- Targeting the NF-κB Pathway in Cancer TherapySurgical Oncology Clinics of North America, 2013
- Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3Proceedings of the National Academy of Sciences of the United States of America, 2013
- Essential role of cooperative NF-κB and Stat3 recruitment to ICAM-1 intronic consensus elements in the regulation of radiation-induced invasion and migration in gliomaOncogene, 2012
- A CXCL1 Paracrine Network Links Cancer Chemoresistance and MetastasisCell, 2012
- Effect of Brain- and Tumor-Derived Connective Tissue Growth Factor on Glioma InvasionJNCI Journal of the National Cancer Institute, 2011
- Radiation-triggered Tumor Necrosis Factor (TNF) α-NFκB Cross-signaling Favors Survival Advantage in Human Neuroblastoma CellsOnline Journal of Public Health Informatics, 2011
- The role of chemokines in intestinal inflammation and cancerCurrent Opinion in Pharmacology, 2009
- Epithelial-Mesenchymal Transitions in Development and DiseaseCell, 2009
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociationNature, 2003