ArticleScience signaling2018
Integrated proximal proteomics reveals IRS2 as a determinant of cell survival in ALK-driven neuroblastoma.
Article in Science signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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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
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- Pooled it
- Systematic review of the receptor tyrosine kinase superfamily in neuroblastoma pathophysiology.Cancer metastasis reviews · 2022Pooled it
- HMMR has oncoprotein-like properties in neuroblastoma cells and high HMMR expression has independent prognostic potential in neuroblastomas.Scientific reports · 2025Article
- Cell-intrinsic insulin signaling defects in human iPS cell-derived hepatocytes in type 2 diabetes.The Journal of clinical investigation · 2025Article
- Unveiling Tumorigenesis Mechanisms and Drug Therapy in Neuroblastoma by Mass Spectrometry Based Proteomics.Children (Basel, Switzerland) · 2024Review
- Anaplastic Lymphoma Kinase signaling stabilizes SLC3A2 expression via MARCH11 to promote neuroblastoma cell growth.Cell death and differentiation · 2024Article
- Anaplastic Lymphoma Kinase signaling stabilizes SLC3A2 expression via MARCH11 to promote neuroblastoma cell growth.Cell death and differentiation · 2024Article
- Preclinical exploration of the DNA damage response pathway using the interactive neuroblastoma cell line explorer CLEAN.NAR cancer · 2024Article
- Preclinical exploration of the DNA damage response pathway using the interactive neuroblastoma cell line explorer CLEAN.NAR cancer · 2024Article
- Phosphorylation Codes in IRS-1 and IRS-2 Are Associated with the Activation/Inhibition of Insulin Canonical Signaling Pathways.Current issues in molecular biology · 2024Review
- Metabolic protein kinase signalling in neuroblastoma.Molecular metabolism · 2023Review
- IGF1R Contributes to Cell Proliferation inCancers · 2023Article
- Collateral lethality between HDAC1 and HDAC2 exploits cancer-specific NuRD complex vulnerabilities.Nature structural & molecular biology · 2023Article
- ALK fusion NSCLC oncogenes promote survival and inhibit NK cell responses viaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Phosphoproteomics of primary AML patient samples reveals rationale for AKT combination therapy and p53 context to overcome selinexor resistance.Cell reports · 2022Article
- Systematic identification of ALK substrates by integrated phosphoproteome and interactome analysis.Life science alliance · 2022Article
- From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma.Journal of personalized medicine · 2021Review
- Synthetic Heterocyclic Derivatives as Kinase Inhibitors Tested for the Treatment of Neuroblastoma.Molecules (Basel, Switzerland) · 2021Review
- Defining Pathological Activities of ALK in Neuroblastoma, a Neural Crest-Derived Cancer.International journal of molecular sciences · 2021Review
- IGF1 receptor inhibition amplifies the effects of cancer drugs by autophagy and immune-dependent mechanisms.Journal for immunotherapy of cancer · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 4 countries.
Funding
Abstract
Oncogenic anaplastic lymphoma kinase (ALK) is one of the few druggable targets in neuroblastoma, and therapy resistance to ALK-targeting tyrosine kinase inhibitors (TKIs) comprises an inevitable clinical challenge. Therefore, a better understanding of the oncogenic signaling network rewiring driven by ALK is necessary to improve and guide future therapies. Here, we performed quantitative mass spectrometry-based proteomics on neuroblastoma cells treated with one of three clinically relevant ALK TKIs (crizotinib, LDK378, or lorlatinib) or an experimentally used ALK TKI (TAE684) to unravel aberrant ALK signaling pathways. Our integrated proximal proteomics (IPP) strategy included multiple signaling layers, such as the ALK interactome, phosphotyrosine interactome, phosphoproteome, and proteome. We identified the signaling adaptor protein IRS2 (insulin receptor substrate 2) as a major ALK target and an ALK TKI-sensitive signaling node in neuroblastoma cells driven by oncogenic ALK. TKI treatment decreased the recruitment of IRS2 to ALK and reduced the tyrosine phosphorylation of IRS2. Furthermore, siRNA-mediated depletion of ALK or IRS2 decreased the phosphorylation of the survival-promoting kinase Akt and of a downstream target, the transcription factor FoxO3, and reduced the viability of three ALK-driven neuroblastoma cell lines. Collectively, our IPP analysis provides insight into the proximal architecture of oncogenic ALK signaling by revealing IRS2 as an adaptor protein that links ALK to neuroblastoma cell survival through the Akt-FoxO3 signaling axis.
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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.