ArticleCell death & disease2020
Targeting tumor cell-derived CCL2 as a strategy to overcome Bevacizumab resistance in ETV5
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 73 citations in OpenAlex.
- Unveiling the Paradoxical Tumor-Suppressive Role of CCL2/CCR2 in Bladder Cancer: A Novel Immunotherapeutic Strategy.Cancers · 2026Article
- Gypenosides inhibit melanoma proliferation, migration and enhance the anti-tumor immunity of CD8Journal of translational medicine · 2026Article
- Epigenetic activation of VEGFA by SMARCD1 mediates tumor progression and bevacizumab resistance in clear cell renal cell carcinoma.BMC cancer · 2026Article
- Article
- The STAT3-ZEB1 axis contributes to CCL2-mediated resistance to osimertinib in lung cancer.Frontiers in oncology · 2026Article
- Cytokine CCL2 secreted by cancer-associated fibroblasts augments temozolomide resistance in glioblastoma through ERK1/2 signaling.Oncogene · 2025Article
- Perineural Invasion in Pancreatic Ductal Adenocarcinoma: Recapitulating Its Importance and Defining Future Directions.United European gastroenterology journal · 2025Review
- Chidamide suppresses macrophage-mediated immune evasion and tumor progression in small cell lung cancer by targeting the STAT4/CCL2 signaling pathway.Cancer biology & medicine · 2025Article
- Transcriptional regulation of ETV5 by mitogen-activated protein kinase via ETS-1 in human pancreatic cancer cells.Scientific reports · 2025Article
- Single-cell sequencing uncovers a high ESM1-expression endothelial cell subpopulation associated with bladder cancer progression and the immunosuppressive microenvironment.Scientific reports · 2025Article
- Enhancing Colorectal Cancer Treatment Through VEGF/VEGFR Inhibitors and Immunotherapy.Current treatment options in oncology · 2025Review
- Identification of Immune Infiltration-Associated CC Motif Chemokine Ligands as Biomarkers and Targets for Colorectal Cancer Prevention and Immunotherapy.International journal of molecular sciences · 2025Article
- Chemokine ligand 2: beyond chemotaxis-a multifaceted role in tumor progression.Frontiers in immunology · 2025Review
- Immune molecule diagnostics in colorectal cancer: CCL2 and CXCL11.Open life sciences · 2025Article
- Targeting Perineural Invasion in Pancreatic Cancer.Cancers · 2024Review
- Genetic and microenvironmental evolution of colorectal liver metastases under chemotherapy.Cell reports. Medicine · 2024Article
- Identification of ETV5 as a prognostic marker related to epigenetic modification in pan-cancer and facilitates tumor progression in hepatocellular carcinoma.Scientific reports · 2024Article
- Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.MedComm · 2024Review
- Article
- Targeting cytokine and chemokine signaling pathways for cancer therapy.Signal transduction and targeted therapy · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In our previous study, ETV5 mediated-angiogenesis was demonstrated to be dependent upon the PDGF-BB/PDGFR-β/Src/STAT3/VEGFA pathway in colorectal cancer (CRC). However, the ability of ETV5 to affect the efficacy of anti-angiogenic therapy in CRC requires further investigation. Gene set enrichment analysis (GSEA) and a series of experiments were performed to identify the critical candidate gene involved in Bevacizumab resistance. Furthermore, the ability of treatment targeting the candidate gene to enhance Bevacizumab sensitivity in vitro and in vivo was investigated. Our results revealed that ETV5 directly bound to the VEGFA promoter to promote translation of VEGFA. However, according to in vitro and in vivo experiments, ETV5 unexpectedly accelerated antiVEGF therapy (Bevacizumab) resistance. GSEA and additional assays confirmed that ETV5 could promote angiogenesis by inducing the secretion of another tumor angiogenesis factor (CCL2) in CRC cells to facilitate Bevacizumab resistance. Mechanistically, ETV5 upregulated CCL2 by activating STAT3 to facilitate binding with the CCL2 promoter. ETV5 induced-VEGFA translation and CCL2 secretion were mutually independent mechanisms, that induced angiogenesis by activating the PI3K/AKT and p38/MAPK signaling pathways in human umbilical vein endothelial cells (HUVECs). In CRC tissues, ETV5 protein levels were positively associated with CD31, CCL2, and VEGFA protein expression. CRC patients possessing high expression of ETV5/VEGFA or ETV5/CCL2 exhibited a poorer prognosis compared to that of other patients. Combined antiCCL2 and antiVEGFA (Bevacizumab) treatment could inhibit tumor angiogenesis and growth more effectively than single treatments in CRCs with high expression of ETV5 (ETV5
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