ArticleProceedings of the National Academy of Sciences of the United States of America2014
Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. 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 69 papers.
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Who cites it
69 citing papers in PubMed, 124 citations in OpenAlex.
- Quantitative phosphoproteomic profiling of CCL5/CCR5 signaling cascade in melanoma cells.Frontiers in oncology · 2026Article
- Spiegelmer Aptamers: Innovative Approach in Breast Cancer.Breast cancer : basic and clinical research · 2026Review
- Molecular basis for the interactions of eIF2β with eIF5, eIF2B, and 5MP1 and their regulation by CK2.RNA (New York, N.Y.) · 2025Article
- A cancer persistent DNA repair circuit driven by MDM2, MDM4 (MDMX), and mutant p53 for recruitment of MDC1 and 53BP1 on chromatin.Nucleic acids research · 2025Article
- Targeting the CXCR4/CXCL12 Axis in Cancer Therapy: Analysis of Recent Advances in the Development of Potential Anticancer Agents.Molecules (Basel, Switzerland) · 2025Review
- A1, an innovative fluorinated CXCR4 inhibitor, redefines the therapeutic landscape in colorectal cancer.Cancer cell international · 2025Article
- Cancer stem cells in personalized therapy: mechanisms, microenvironment crosstalk, and therapeutic vulnerabilities.Frontiers in cell and developmental biology · 2025Review
- Phosphorylation regulates the chromatin remodeler SMARCAD1 in nucleosome binding, ATP hydrolysis, and histone exchange.The Journal of biological chemistry · 2024Article
- SAP deletion promotes malignant insulinoma progression by inducing CXCL12 secretion from CAFs via the CXCR4/p38/ERK signalling pathway.Journal of cellular and molecular medicine · 2024Article
- CDKN1A/p21 in Breast Cancer: Part of the Problem, or Part of the Solution?International journal of molecular sciences · 2023Review
- Mass spectrometry-based phosphoproteomics in clinical applications.Trends in analytical chemistry : TRAC · 2023Article
- Tissue-specific cancer stem/progenitor cells: Therapeutic implications.World journal of stem cells · 2023Review
- Comprehensive Metabolic Profiling and Genome-wide Analysis Reveal Therapeutic Modalities for Hepatocellular Carcinoma.Research (Washington, D.C.) · 2023Article
- Tumour Stem Cells in Breast Cancer.International journal of molecular sciences · 2022Review
- Review
- Breast Cancer Stem-Like Cells in Drug Resistance: A Review of Mechanisms and Novel Therapeutic Strategies to Overcome Drug Resistance.Frontiers in oncology · 2022Review
- Article
- Application of a small molecule inhibitor screen approach to identify CXCR4 downstream signaling pathways that promote a mesenchymal and fulvestrant-resistant phenotype in breast cancer cells.Oncology letters · 2021Article
- Dysregulation of phosphoproteins in hepatocellular carcinoma revealed via quantitative analysis of the phosphoproteome.Oncology letters · 2021Article
- β-arrestin mediates communication between plasma membrane and intracellular GPCRs to regulate signaling.Communications biology · 2020Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Breast cancer is the leading cause of cancer-related mortality in women worldwide, with an estimated 1.7 million new cases and 522,000 deaths around the world in 2012 alone. Cancer stem cells (CSCs) are essential for tumor reoccurrence and metastasis which is the major source of cancer lethality. G protein-coupled receptor chemokine (C-X-C motif) receptor 4 (CXCR4) is critical for tumor metastasis. However, stromal cell-derived factor 1 (SDF-1)/CXCR4-mediated signaling pathways in breast CSCs are largely unknown. Using isotope reductive dimethylation and large-scale MS-based quantitative phosphoproteome analysis, we examined protein phosphorylation induced by SDF-1/CXCR4 signaling in breast CSCs. We quantified more than 11,000 phosphorylation sites in 2,500 phosphoproteins. Of these phosphosites, 87% were statistically unchanged in abundance in response to SDF-1/CXCR4 stimulation. In contrast, 545 phosphosites in 266 phosphoproteins were significantly increased, whereas 113 phosphosites in 74 phosphoproteins were significantly decreased. SDF-1/CXCR4 increases phosphorylation in 60 cell migration- and invasion-related proteins, of them 43 (>70%) phosphoproteins are unrecognized. In addition, SDF-1/CXCR4 upregulates the phosphorylation of 44 previously uncharacterized kinases, 8 phosphatases, and 1 endogenous phosphatase inhibitor. Using computational approaches, we performed system-based analyses examining SDF-1/CXCR4-mediated phosphoproteome, including construction of kinase-substrate network and feedback regulation loops downstream of SDF-1/CXCR4 signaling in breast CSCs. We identified a previously unidentified SDF-1/CXCR4-PKA-MAP2K2-ERK signaling pathway and demonstrated the feedback regulation on MEK, ERK1/2, δ-catenin, and PPP1Cα in SDF-1/CXCR4 signaling in breast CSCs. This study gives a system-wide view of phosphorylation events downstream of SDF-1/CXCR4 signaling in breast CSCs, providing a resource for the study of CSC-targeted cancer therapy.
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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.