ArticleCells2022
The CXCL12/CXCR4/ACKR3 Signaling Axis Regulates PKM2 and Glycolysis.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Changes in the metabolism of axillary lymph node cells as a predictor of regional metastasis in breast cancer.World journal of experimental medicine · 2026Article
- [European journal of nuclear medicine and molecular imaging · 2026Article
- Early multi-omic signatures and machine learning models predict cardiomyocyte differentiation efficiency and enable robust hPSC differentiation to cardiomyocytes.bioRxiv : the preprint server for biology · 2026Article
- Augment proteasome inhibitor efficacy activates CD8Cell reports. Medicine · 2025Article
- CXCL12 links bladder cancer and diabetes as a potential biomarker.Scientific reports · 2025Article
- Warburg-like Metabolic Reprogramming in Endometriosis: From Molecular Mechanisms to Therapeutic Approaches.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Utilizing bioinformatics and machine learning to identify CXCR4 gene-related therapeutic targets in diabetic foot ulcers.Frontiers in endocrinology · 2025Article
- Osteoarthritis Bone Marrow MSCs Retain Regenerative Competence and Chemokine Responsiveness for Drug-Based In Situ Tissue Engineering.Stem cells international · 2025Article
- Single-cell sequencing reveals cellular heterogeneity of nucleus pulposus in intervertebral disc degeneration.Scientific reports · 2024Article
- Cancer-associated fibroblasts: challenges and opportunities.Oncotarget · 2023Article
- Analysis of C-X-C motif chemokine receptors in breast cancer: potential value in immunotherapy and prognostic prediction.Annals of translational medicine · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In response to CXCL12, CXCR4 and ACKR3 both recruit β-arrestin 2, regulating the assembly of interacting proteins that drive signaling and contribute to the functions of both receptors in cancer and multiple other diseases. A prior proteomics study revealed that β-arrestin 2 scaffolds pyruvate kinase M2 (PKM2), an enzyme implicated in shifting cells to glycolytic metabolism and poor prognosis in cancer. We hypothesized that CXCL12 signaling regulates PKM2 protein interactions, oligomerization, and glucose metabolism. We used luciferase complementation in cell-based assays and a tumor xenograft model of breast cancer in NSG mice to quantify how CXCR4 and ACKR3 change protein interactions in the β-arrestin-ERK-PKM2 pathway. We also used mass spectrometry to analyze the effects of CXCL12 on glucose metabolism. CXCL12 signaling through CXCR4 and ACKR3 stimulated protein interactions among β-arrestin 2, PKM2, ERK2, and each receptor, leading to the dissociation of PKM2 from β-arrestin 2. The activation of both receptors reduced the oligomerization of PKM2, reflecting a shift from tetramers to dimers or monomers with low enzymatic activity. Mass spectrometry with isotopically labeled glucose showed that CXCL12 signaling increased intermediate metabolites in glycolysis and the pentose phosphate pathway, with ACKR3 mediating greater effects. These data establish how CXCL12 signaling regulates PKM2 and reprograms cellular metabolism.
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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.