ArticleCell death & disease2019
A positive feedback loop of β-catenin/CCR2 axis promotes regorafenib resistance in colorectal cancer.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 35 citations in OpenAlex.
- From bud to stem: dynamics of hematopoietic stem cells that drive homing and mobilization.Current opinion in hematology · 2026Review
- Overcoming Regorafenib Resistance in Colorectal Cancer: Synergistic Efficacy of Cilengitide in HT29 and WiDr Cells.Medeniyet medical journal · 2026Article
- Macrophages in Colorectal Cancer: from Normal Mucosa to Distant Metastasis: Beyond the M1/M2 Paradigm.Journal of Cancer · 2026Review
- Cooperative CCL2/CCR2 and HGF/MET signaling enhances breast cancer growth and invasion associated with metabolic reprogramming.Cancer biology & therapy · 2025Article
- Piperlongumine overcomes osimertinib resistance via governing ubiquitination-modulated Sp1 turnover.JCI insight · 2025Article
- Review
- Regorafenib in Patients With Solid Tumors WithJCO precision oncology · 2024Article
- Review
- NCF1-dependent production of ROS protects against lupus by regulating plasmacytoid dendritic cell development and functions.JCI insight · 2023Article
- Tumors of the Digestive System: Comprehensive Review of Ancillary Testing and Biomarkers in the Era of Precision Medicine.Current oncology (Toronto, Ont.) · 2023Review
- Article
- Senescent neutrophils-derived exosomal piRNA-17560 promotes chemoresistance and EMT of breast cancer via FTO-mediated m6A demethylation.Cell death & disease · 2022Article
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- Combination of FOXD1 and Plk2: A novel biomarker for predicting unfavourable prognosis of colorectal cancer.Journal of cellular and molecular medicine · 2022Article
- Crosstalk between β-Catenin and CCL2 Drives Migration of Monocytes towards Glioblastoma Cells.International journal of molecular sciences · 2022Article
- KLF5 inhibition overcomes oxaliplatin resistance in patient-derived colorectal cancer organoids by restoring apoptotic response.Cell death & disease · 2022Article
- Noncoding RNAs in Drug Resistance of Gastrointestinal Stromal Tumor.Frontiers in cell and developmental biology · 2022Review
- Icariin attenuates the tumor growth by targeting miR-1-3p/TNKS2/Wnt/β-catenin signaling axis in ovarian cancer.Frontiers in oncology · 2022Article
- TOP2A inhibition reverses drug resistance of hepatocellular carcinoma to regorafenib.American journal of cancer research · 2022Article
- Macrophages play a role in inflammatory transformation of colorectal cancer.World journal of gastrointestinal oncology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to molecular targeted therapies is a significant challenge for advanced colorectal cancer (CRC). Understanding the underlying mechanisms and developing effective strategies against regorafenib resistance are highly desired in the clinic. Here, we screened the expression of chemokine receptors and identified CC chemokine receptor 2 (CCR2) as a top upregulated gene in regorafenib-resistant cells. CCR2 silencing alleviated drug tolerance in regorafenib-resistant cells, while overexpression of CCR2 enhanced CRC cells resistance to regorafenib. Moreover, CCR2-mediated regorafenib tolerance was demonstrated to be associated with AKT/GSK3β-regulated β-catenin stabilization. In turn, β-catenin modulation is sufficient to trigger the transcriptional activation of CCR2 expression. Clinically, high-CCR2 expression was correlated to shorter overall survival and disease-free survival of patients. A positive correlation between CCR2 and nuclear β-catenin expression was observed in a cohort of CRC tissues. Altogether, these findings suggest β-catenin and CCR2 are part of a positive-feedback loop, which sustains a high CCR2 expression level, conferring CRC cells resistance to regorafenib. Thus, targeting CCR2 may be a useful therapeutic strategy to alleviate regorafenib tolerance to increase the efficacy of CRC treatments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.