ArticleCell death & disease2021
CXCR4 intracellular protein promotes drug resistance and tumorigenic potential by inversely regulating the expression of Death Receptor 5.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 61 citations in OpenAlex.
- Immunoexpression of CXCL12 and CXCR4 in giant cell granulomas of the jaws and giant cell tumor of bone.Medicina oral, patologia oral y cirugia bucal · 2026Article
- Physical interaction with Ephrin B1 promotes CXCR4 intracellular localization and oncogenic potential.Cellular and molecular life sciences : CMLS · 2026Article
- G-CSF promotes H3K27ac-modified KLF5 to activate CXCR4 expression and drive colon cancer growth and metastasis.European journal of medical research · 2026Article
- Steroidal Alkaloids fromACS omega · 2025Article
- Yin Yang 1 (YY1) as a Central Node in Drug Resistance Pathways: Potential for Combination Strategies in Cancer Therapy.Biomolecules · 2025Review
- Disruption of constitutive CXCR4 oligomers impairs oncogenic properties in lymphoid neoplasms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting YY1-DR5 Axis by Pyripyropene O as a Novel Therapeutic Strategy Against Prostate Cancer: Molecular Mechanisms and In Vivo Zebrafish Validation.Marine drugs · 2025Article
- Comparison of Differences in Cell Migration during the Osteogenic and Adipogenic Differentiation of the Bone Marrow-Derived Stem Cells.Journal of bone metabolism · 2025Article
- CXCR4/CXCL12 blockade therapy; a new horizon in TNBC therapy.Medical oncology (Northwood, London, England) · 2025Review
- Immunoexpression of CXCL12 and CXCR4 in oral tongue squamous cell carcinoma of young and older patients.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Article
- Expression of CXCR4 in the Primary Lesion of Recurrent Metastatic Breast Cancer and Its Association With Prognosis.International journal of general medicine · 2025Article
- NF-κB pathway and angiogenesis: insights into colorectal cancer development and therapeutic targets.European journal of medical research · 2024Review
- A computational approach to assessing the prognostic implications of BRAF and RAS mutations in patients with papillary thyroid carcinoma.Endocrine · 2024Article
- Identifying and Assessing Putative Allosteric Sites and Modulators for CXCR4 Predicted through Network Modeling and Site Identification by Ligand Competitive Saturation.The journal of physical chemistry. B · 2024Article
- Comprehensive summary: the role of PBX1 in development and cancers.Frontiers in cell and developmental biology · 2024Review
- Sec1 regulates intestinal mucosal immunity in a mouse model of inflammatory bowel disease.BMC immunology · 2023Article
- CXC chemokine receptor 4 (CXCR4) blockade in cancer treatment.Journal of cancer research and clinical oncology · 2023Review
- Targeting CXCR4 abrogates resistance to trastuzumab by blocking cell cycle progression and synergizes with docetaxel in breast cancer treatment.Breast cancer research : BCR · 2023Article
- Differential Expression and Clinical Relevance of C-X-C Motif Chemokine Receptor 4 (CXCR4) in Renal Cell Carcinomas, Benign Renal Tumors, and Metastases.International journal of molecular sciences · 2023Article
- Targeting CXCR4 abrogates resistance to trastuzumab by blocking cell cycle progression and synergizes with docetaxel in breast cancer treatment.Research square · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemokine receptor CXCR4 overexpression in solid tumors has been strongly associated with poor prognosis and adverse clinical outcome. However, blockade of CXCL12-CXCR4 signaling axis by inhibitors like Nox-A12, FDA approved CXCR4 inhibitor drug AMD3100 have shown limited clinical success in cancer treatment. Therefore, exclusive contribution of CXCR4-CXCL12 signaling in pro-tumorigenic function is questionable. In our pursuit to understand the impact of chemokine signaling in carcinogenesis, we reveal that instead of CXCR4-CXCL12 signaling, presence of CXCR4 intracellular protein augments paclitaxel resistance and pro-tumorigenic functions. In search of pro-apoptotic mechanisms for CXCR4 mediated drug resistance; we discover that DR5 is a new selective target of CXCR4 in breast and colon cancer. Further, we detect that CXCR4 directs the differential recruitment of transcription factors p53 and YY1 to the promoter of DR5 in course of its transcriptional repression. Remarkably, inhibiting CXCR4-ligand-mediated signals completely fails to block the above phenotype. Overexpression of different mutant versions of CXCR4 lacking signal transduction capabilities also result in marked downregulation of DR5 expression in colon cancer indeed confirms the reverse relationship between DR5 and intracellular CXCR4 protein expression. Irrespective of CXCR4 surface expression, by utilizing stable gain and loss of function approaches, we observe that intracellular CXCR4 protein selectively resists and sensitizes colon cancer cells against paclitaxel therapy in vitro and in vivo. Finally, performing TCGA data mining and using human breast cancer patient samples, we demonstrate that expression of CXCR4 and DR5 are inversely regulated. Together, our data suggest that targeting CXCR4 intracellular protein may be critical to dampen the pro-tumorigenic functions of CXCR4.
Indexed as
Identifiers
What OpenQuestion holds
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.