ArticleMolecular and cellular biology2013
The membrane-proximal KXGFFKR motif of α-integrin mediates chemoresistance.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
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- Research progress on the regulatory mechanism of integrin-mediated mechanical stress in cells involved in bone metabolism.Journal of cellular and molecular medicine · 2024Review
- A specialized integrin-binding motif enables proTGF-β2 activation by integrin αVβ6 but not αVβ8.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Novel Functions of Integrins as Receptors of CD154: Their Role in Inflammation and Apoptosis.Cells · 2022Review
- Dermal fibroblasts promote cancer cell proliferation and exhibit fibronectin overexpression in early mycosis fungoides.Journal of dermatological science · 2022Article
- VLA-4 Induces Chemoresistance of T Cell Acute Lymphoblastic Leukemia Cells via PYK2-Mediated Drug Efflux.Cancers · 2021Article
- Cancer Biology of the Endoplasmic Reticulum Lectin Chaperones Calreticulin, Calnexin and PDIA3/ERp57.Progress in molecular and subcellular biology · 2021Review
- Dual Targeting of Stromal Cell Support and Leukemic Cell Growth by a Peptidic PKC Inhibitor Shows Effectiveness against B-ALL.International journal of molecular sciences · 2020Article
- Cadherins, Selectins, and Integrins in CAM-DR in Leukemia.Frontiers in oncology · 2020Review
- Cell adhesion to collagen promotes leukemia resistance to doxorubicin by reducing DNA damage through the inhibition of Rac1 activation.Scientific reports · 2019Article
- Beta1 integrin blockade overcomes doxorubicin resistance in human T-cell acute lymphoblastic leukemia.Cell death & disease · 2019Article
- Integrins and ERp57 Coordinate to Regulate Cell Surface Calreticulin in Immunogenic Cell Death.Frontiers in oncology · 2019Article
- Endoplasmic reticulum in health and disease: the 12th International Calreticulin Workshop, Delphi, Greece.Journal of cellular and molecular medicine · 2017Article
- Eviction from the sanctuary: Development of targeted therapy against cell adhesion molecules in acute lymphoblastic leukemia.Seminars in oncology · 2017Review
- α-Integrin expression and function modulates presentation of cell surface calreticulin.Cell death & disease · 2016Article
- Article
- β1 Integrins as Therapeutic Targets to Disrupt Hallmarks of Cancer.Frontiers in pharmacology · 2015Review
- New Abelson interactor-1 (Abi-1)-driven mechanism of acquired drug resistance.Leukemia supplements · 2014Article
- Role of integrin alpha4 in drug resistance of leukemia.Frontiers in oncology · 2014Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cell adhesion-mediated drug resistance contributes to minimal residual disease and relapse in hematological malignancies. Here, we show that adhesion of Jurkat T-acute lymphoblastic leukemia cells to substrates engaging α4β1-integrin or α5β1-integrin promotes chemoresistance to doxorubicin-induced apoptosis. Reconstituted expression of α4δ, a truncated α4-integrin with KXGFFKR as the cytoplasmic motif, in α4-deficient cells promoted chemoresistance to doxorubicin in a manner independent of α4-mediated adhesion. The adhesion-independent chemoresistance did not require β1-integrin as the heterodimeric pair, since expression of Tacδ, a monomeric nonintegrin transmembrane protein fused to the juxtamembrane KXGFFKR, was sufficient to reproduce the phenomenon. The requirement for integrin-mediated adhesion in stimulation of Akt phosphorylation and activation was bypassed for cells expressing α4δ and Tacδ. Cells expressing α4δ and Tacδ exhibited a high influx of extracellular Ca(2+), and inhibition of Ca(2+) channels with verapamil attenuated the adhesion-independent chemoresistance. Tacδ cells also exhibited greater rates of drug efflux. α4δ and Tacδ interacted with the Ca(2+)-binding protein calreticulin, in a manner dependent on the KXGFFKR motif. Adhesion-mediated engagement of α4-integrins promoted an increased calreticulin-α4 association and greater influx of extracellular Ca(2+) than in nonadherent cells. The α-integrin KXGFFKR motif is involved in adhesion-mediated control of chemoresistance in T cells.
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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.