ArticleScience signaling2019
Short-term cellular memory tunes the signaling responses of the chemokine receptor CXCR4.
Article in Science signaling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Quantitative Spatiotemporal Analysis of Intracellular Kinase Activity in Metastatic Breast Cancer Cells Using a Microfluidic-Based Lateral Diffusion Assay.Analytical chemistry · 2026Article
- Mechanisms of resistance to bruton's tyrosine kinase inhibitors: synergistic effects of tumor microenvironment regulation and signaling pathways.Annals of hematology · 2026Review
- Inference of weak-form partial differential equations describing migration and proliferation mechanisms in wound healing experiments on cancer cells.PLoS computational biology · 2025Article
- Substrate stiffness regulates triple-negative breast cancer signaling through CXCR4 receptor dynamics.Scientific reports · 2025Article
- Inhibiting CXCR4 reduces immunosuppressive effects of myeloid cells in breast cancer immunotherapy.Scientific reports · 2025Article
- Characterizing heterogeneous single-cell dose responses computationally and experimentally using threshold inhibition surfaces and dose-titration assays.NPJ systems biology and applications · 2024Article
- Integrating inverse reinforcement learning into data-driven mechanistic computational models: a novel paradigm to decode cancer cell heterogeneity.Frontiers in systems biology · 2024Article
- Optimal phenotypic adaptation in fluctuating environments.Biophysical journal · 2023Article
- Oscillatory ERK Signaling and Morphology Determine Heterogeneity of Breast Cancer Cell Chemotaxis via MEK-ERK and p38-MAPK Signaling Pathways.Bioengineering (Basel, Switzerland) · 2023Article
- Computational modeling implicates protein scaffolding in p38 regulation of Akt.Journal of theoretical biology · 2022Article
- Crosstalk between CXCR4/ACKR3 and EGFR Signaling in Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Emergence of synchronized multicellular mechanosensing from spatiotemporal integration of heterogeneous single-cell information transfer.Cell systems · 2022Article
- MIF/CXCR4 signaling axis contributes to survival, invasion, and drug resistance of metastatic neuroblastoma cells in the bone marrow microenvironment.BMC cancer · 2022Article
- Ultrasound-Induced Mechanical Compaction in Acoustically Responsive Scaffolds Promotes Spatiotemporally Modulated Signaling in Triple Negative Breast Cancer.Advanced healthcare materials · 2022Article
- Article
- Single-cell imaging of ERK and Akt activation dynamics and heterogeneity induced by G-protein-coupled receptors.Journal of cell science · 2022Article
- Pre-existing Cell States Control Heterogeneity of Both EGFR and CXCR4 Signaling.Cellular and molecular bioengineering · 2021Article
- Article
- Modulation of CXCR4-Mediated Gi1 Activation by EGF Receptor and GRK2.ACS pharmacology & translational science · 2020Article
- Targeting disseminated estrogen-receptor-positive breast cancer cells in bone marrow.Oncogene · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The chemokine receptor CXCR4 regulates fundamental processes in development, normal physiology, and diseases, including cancer. Small subpopulations of CXCR4-positive cells drive the local invasion and dissemination of malignant cells during metastasis, emphasizing the need to understand the mechanisms controlling responses at the single-cell level to receptor activation by the chemokine ligand CXCL12. Using single-cell imaging, we discovered that short-term cellular memory of changes in environmental conditions tuned CXCR4 signaling to Akt and ERK, two kinases activated by this receptor. Conditioning cells with growth stimuli before CXCL12 exposure increased the number of cells that initiated CXCR4 signaling and the amplitude of Akt and ERK activation. Data-driven, single-cell computational modeling revealed that growth factor conditioning modulated CXCR4-dependent activation of Akt and ERK by decreasing extrinsic noise (preexisting cell-to-cell differences in kinase activity) in PI3K and mTORC1. Modeling established mTORC1 as critical for tuning single-cell responses to CXCL12-CXCR4 signaling. Our single-cell model predicted how combinations of extrinsic noise in PI3K, Ras, and mTORC1 superimposed on different driver mutations in the ERK and/or Akt pathways to bias CXCR4 signaling. Computational experiments correctly predicted that selected kinase inhibitors used for cancer therapy shifted subsets of cells to states that were more permissive to CXCR4 activation, suggesting that such drugs may inadvertently potentiate pro-metastatic CXCR4 signaling. Our work establishes how changing environmental inputs modulate CXCR4 signaling in single cells and provides a framework to optimize the development and use of drugs targeting this signaling pathway.
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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.