ArticleChembiochem : a European journal of chemical biology2023
Differential Chemoproteomics Reveals MARK2/3 as Cell Migration-Relevant Targets of the ALK Inhibitor Brigatinib.
Article in Chembiochem : a European journal of chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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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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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
4 citing papers in PubMed, 5 citations in OpenAlex.
- Unravelling the Phosphorylation Landscape of Anthrax Toxin Receptor 1: Mechanisms and Functional Insights Through Phosphoproteomic Data Integration.The protein journal · 2025Article
- [Recent Advances in the Treatment of Non-small Cell Lung Cancer with Brigatinib].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Role of MARK2 in the nervous system and cancer.Cancer gene therapy · 2024Review
- Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions.Biomedicines · 2024Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Metastasis poses a major challenge in cancer management, including EML4-ALK-rearranged non-small cell lung cancer (NSCLC). As cell migration is a critical step during metastasis, we assessed the anti-migratory activities of several clinical ALK inhibitors in NSCLC cells and observed differential anti-migratory capabilities despite similar ALK inhibition, with brigatinib displaying superior anti-migratory effects over other ALK inhibitors. Applying an unbiased in situ mass spectrometry-based chemoproteomics approach, we determined the proteome-wide target profile of brigatinib in EML4-ALK+ NSCLC cells. Dose-dependent and cross-competitive chemoproteomics suggested MARK2 and MARK3 as relevant brigatinib kinase targets. Functional validation showed that combined pharmacological inhibition or genetic modulation of MARK2/3 inhibited cell migration. Consistently, brigatinib treatment induced inhibitory YAP1 phosphorylation downstream of MARK2/3. Collectively, our data suggest that brigatinib exhibits unusual cross-phenotype polypharmacology as, despite similar efficacy for inhibiting EML4-ALK-dependent cell proliferation as other ALK inhibitors, it more effectively prevented migration of NSCLC cells due to co-targeting of MARK2/3.
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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.