ArticleThe Journal of experimental medicine2002
Crosstalk between BCR/ABL oncoprotein and CXCR4 signaling through a Src family kinase in human leukemia cells.
Article in The Journal of experimental medicine, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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
36 citing papers in PubMed, 104 citations in OpenAlex.
- 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
- Profiles of autophagy-related genes in esophageal adenocarcinoma.BMC cancer · 2020Article
- Synergism between IL7R and CXCR4 drives BCR-ABL induced transformation in Philadelphia chromosome-positive acute lymphoblastic leukemia.Nature communications · 2020Article
- ACLY is the novel signaling target of PIPHeliyon · 2020Article
- Essential Role of Lyn in Fibrosis.Frontiers in physiology · 2016Article
- A critical role of Src family kinase in SDF-1/CXCR4-mediated bone-marrow progenitor cell recruitment to the ischemic heart.Journal of molecular and cellular cardiology · 2015Article
- Neutrophil migration: moving from zebrafish models to human autoimmunity.Immunological reviews · 2013Review
- Article
- Effects of plerixafor in combination with BCR-ABL kinase inhibition in a murine model of CML.Blood · 2012Article
- Role of stromal microenvironment in nonpharmacological resistance of CML to imatinib through Lyn/CXCR4 interactions in lipid rafts.Leukemia · 2012Article
- Dasatinib inhibits CXCR4 signaling in chronic lymphocytic leukaemia cells and impairs migration towards CXCL12.PloS one · 2012Article
- Tyrosine kinase chromosomal translocations mediate distinct and overlapping gene regulation events.BMC cancer · 2011Article
- Mechanisms regulating chemokine receptor activity.Immunology · 2011Review
- Article
- Src-family and Syk kinases in activating and inhibitory pathways in innate immune cells: signaling cross talk.Cold Spring Harbor perspectives in biology · 2011Review
- Abl kinases are required for invadopodia formation and chemokine-induced invasion.The Journal of biological chemistry · 2010Article
- CXCR4-mediated bone marrow progenitor cell maintenance and mobilization are modulated by c-kit activity.Circulation research · 2010Article
- Inhibition of class II phosphoinositide 3-kinase gamma expression by p185(Bcr-Abl) contributes to impaired chemotaxis and aberrant homing of leukemic cells.Leukemia & lymphoma · 2010Article
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Stromal-derived factor (SDF)-1 and its G protein-coupled receptor, CXCR4, regulate stem/progenitor cell migration and retention in the marrow and are required for hematopoiesis. We show here an interaction between CXCR4 and the Src-related kinase, Lyn, in normal progenitors. We demonstrate that CXCR4-dependent stimulation of Lyn is associated with the activation of phosphatidylinositol 3-kinase (PI3-kinase). This chemokine signaling, which involves a Src-related kinase and PI3-kinase, appears to be a target for BCR/ABL, a fusion oncoprotein expressed only in leukemia cells. We show that the binding of phosphorylated BCR/ABL to Lyn results in the constitutive activation of Lyn and PI3-kinase, along with a total loss of responsiveness of these kinases to SDF-1 stimulation. Inhibition of BCR/ABL tyrosine kinase with STI571 restores Lyn responsiveness to SDF-1 signaling. Thus, BCR/ABL perturbs Lyn function through a tyrosine kinase-dependent mechanism. Accordingly, the blockade of Lyn tyrosine kinase inhibits both BCR/ABL-dependent and CXCR4-dependent cell movements. Our results demonstrate, for the first time, that Lyn-mediated pathological crosstalk exists between BCR/ABL and the CXCR4 pathway in leukemia cells, which disrupts chemokine signaling and chemotaxis, and increases the ability of immature cells to escape from the marrow. These results define a Src tyrosine kinases-dependent mechanism whereby BCR/ABL (and potentially other oncoproteins) dysregulates G protein-coupled receptor signaling and function of mammalian precursors.
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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.