ArticleScientific reports2016
The use of cellular thermal shift assay (CETSA) to study Crizotinib resistance in ALK-expressing human cancers.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 53 citations in OpenAlex.
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- A superior loading control for the cellular thermal shift assay.Scientific reports · 2022Article
- Ziprasidone suppresses pancreatic adenocarcinoma cell proliferation by targeting GOT1 to trigger glutamine metabolism reprogramming.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Extracellular domain shedding of the ALK receptor mediates neuroblastoma cell migration.Cell reports · 2021Article
- How Physiologic Targets Can Be Distinguished from Drug-Binding Proteins.Molecular pharmacology · 2021Article
- Receptor tyrosine kinases and cancer: oncogenic mechanisms and therapeutic approaches.Oncogene · 2021Review
- A regulatory region on RIPK2 is required for XIAP binding and NOD signaling activity.EMBO reports · 2020Article
- Activation of IGF-1R pathway and NPM-ALK G1269A mutation confer resistance to crizotinib treatment in NPM-ALK positive lymphoma.Investigational new drugs · 2020Article
- Drug repurposing: a promising tool to accelerate the drug discovery process.Drug discovery today · 2019Review
- Drug repurposing: progress, challenges and recommendations.Nature reviews. Drug discovery · 2019Review
- The absence of a novel intron 19-retainingOncotarget · 2018Article
- A natural inhibitor of kidney-type glutaminase: a withanolide fromOncotarget · 2017Article
- High expression of β-catenin contributes to the crizotinib resistant phenotype in the stem-like cell population in neuroblastoma.Scientific reports · 2017Article
- Farnesyl phenolic enantiomers as natural MTH1 inhibitors fromOncotarget · 2017Article
- Novel Molecular Challenges in Targeting Anaplastic Lymphoma Kinase in ALK-Expressing Human Cancers.Cancers · 2017Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 5 countries.
Funding
Abstract
Various forms of oncogenic ALK proteins have been identified in various types of human cancers. While Crizotinib, an ALK inhibitor, has been found to be therapeutically useful against a subset of ALK(+) tumours, clinical resistance to this drug has been well recognized and the mechanism of this phenomenon is incompletely understood. Using the cellular thermal shift assay (CETSA), we measured the Crizotinib-ALK binding in a panel of ALK(+) cell lines, and correlated the findings with the ALK structure and its interactions with specific binding proteins. The Crizotinib IC50 significantly correlated with Crizotinib-ALK binding. The suboptimal Crizotinib-ALK binding in Crizotinib-resistant cells is not due to the cell-specific environment, since transfection of NPM-ALK into these cells revealed substantial Crizotinib-NPM-ALK binding. Interestingly, we found that the resistant cells expressed higher protein level of β-catenin and siRNA knockdown restored Crizotinib-ALK binding (correlated with a significant lowering of IC50). Computational analysis of the crystal structures suggests that β-catenin exerts steric hindrance to the Crizotinib-ALK binding. In conclusion, the Crizotinib-ALK binding measurable by CETSA is useful in predicting Crizotinib sensitivity, and Crizotinib-ALK binding is in turn dictated by the structure of ALK and some of its binding partners.
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