ArticleOncotarget2012
A novel co-operative mechanism linking TGFβ and Lyn kinase activation to imatinib resistance in chronic myeloid leukaemia cells.
Article in Oncotarget, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- E3 Ubiquitin Ligase in Anticancer Drugdsla Resistance: Recent Advances and Future Potential.Frontiers in pharmacology · 2021Review
- Signaling Pathways in Leukemic Stem Cells.Advances in experimental medicine and biology · 2019Review
- Association between Altered Expression and Genetic Variations of Transforming Growth Factor β-Smad Pathway with Chronic Myeloid Leukemia.International journal of hematology-oncology and stem cell research · 2018Article
- Ductular reaction correlates with fibrogenesis but does not contribute to liver regeneration in experimental fibrosis models.PloS one · 2017Article
- Article
- Genomic quantitative real-time PCR proves residual disease positivity in more than 30% samples with negative mRNA-based qRT-PCR in Chronic Myeloid Leukemia.Oncoscience · 2014Article
- Lyn mitigates mouse airway remodeling by downregulating the TGF-β3 isoform in house dust mite models.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Combined effects of PI3K and SRC kinase inhibitors with imatinib on intracellular calcium levels, autophagy, and apoptosis in CML-PBL cells.Cell cycle (Georgetown, Tex.) · 2013Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The advent of a mechanism specific inhibitor imatinib, targeting Bcr-Abl kinase, has paved the way for new treatment strategies in chronic myeloid leukaemia (CML). However, resistance to imatinib is common in patients and has recently been linked to both transforming growth factor-β (TGFβ) and elevated Lyn kinase activity, although molecular mechanisms remain largely unknown. Here, using leukaemic MYL cell lines derived from CML patients, we show that TGFβ plays a key role in imatinib-resistance via direct effects on Lyn ubiquitination and turnover that results in bursts of Lyn kinase activity, and identify c-cbl is a candidate E3 ubiquitin ligase. Furthermore, blockade of TGFβ signalling activity with the TGFβ receptor kinase inhibitor SB431542 significantly reduces Lyn turnover and activation, and subsequently enhances imatinib-mediated CML cell death in a proteasomal-dependent manner. Collectively, our data reveals novel co-operative mechanisms in CML involving TGFβ and Lyn kinase linked to proteasome function and ubiquitination, and thus supports therapeutic approaches that target TGFβ pathway activity as a strategy for overcoming imatinib-resistance in CML.
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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.