ArticleeLife2021
Extracellular signal-regulated kinase mediates chromatin rewiring and lineage transformation in lung cancer.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
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- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- Synthesis and Development of 3-((2,4-Difluorophenyl)Amino)Propanoic Acid Derivatives as an Antiproliferative Medicinal Chemistry Scaffold Targeting Growth Factor Receptors.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Eukaryote initiation factor 6 modulates small-cell lung carcinoma plasticity via the integrin-FAK signaling axis.Nature communications · 2026Article
- EGFR-mutant transformed small cell lung cancer harbors intratumoral heterogeneity targetable with MEK inhibitor combination therapy.JCI insight · 2026Article
- Persistent lineage plasticity driving lung cancer development and progression.Clinical and translational medicine · 2025Review
- Drug tolerance and persistence to EGFR inhibitor treatment are mediated by an ILK-SFK-YAP signaling axis in lung adenocarcinoma.Oncogene · 2025Article
- KSR2 Promotes Self-Renewal and Clonogenicity of Small Cell Lung Carcinoma.Molecular cancer research : MCR · 2025Article
- Molecular basis and therapeutic implications of binary YAPOn/YAPOff cancer classes.The Biochemical journal · 2025Review
- Identification of 3-[(4-Acetylphenyl)(4-Phenylthiazol-2-Yl)Amino]Propanoic Acid Derivatives as Promising Scaffolds for the Development of Novel Anticancer Candidates Targeting SIRT2 and EGFR.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Lethal co-expression intolerance underlies the mutually exclusive expression of ASCL1 and NEUROD1 in SCLC cells.NPJ precision oncology · 2025Article
- Review
- Alectinib combined with cobimetinib in ALK-Rearranged lung Cancer: A phase IB study.Lung cancer (Amsterdam, Netherlands) · 2025Article
- ASCL1 Restrains ERK1/2 to Promote Survival of a Subset of Neuroendocrine Lung Cancers.Molecular cancer therapeutics · 2024Article
- Article
- Role of CDK4/6 inhibitors in targeting Rb proficient small cell lung cancer.Translational lung cancer research · 2024Article
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- Single-Cell Evolutionary Analysis Reveals Drivers of Plasticity and Mediators of Chemoresistance in Small Cell Lung Cancer.Molecular cancer research : MCR · 2023Article
- Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer.Cancer cell · 2023Article
- Characterizing the secretome of EGFR mutant lung adenocarcinoma.Frontiers in oncology · 2023Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Lineage transformation between lung cancer subtypes is a poorly understood phenomenon associated with resistance to treatment and poor patient outcomes. Here, we aimed to model this transition to define underlying biological mechanisms and identify potential avenues for therapeutic intervention. Small cell lung cancer (SCLC) is neuroendocrine in identity and, in contrast to non-SCLC (NSCLC), rarely contains mutations that drive the MAPK pathway. Likewise, NSCLCs that transform to SCLC concomitantly with development of therapy resistance downregulate MAPK signaling, suggesting an inverse relationship between pathway activation and lineage state. To test this, we activated MAPK in SCLC through conditional expression of mutant KRAS or EGFR, which revealed suppression of the neuroendocrine differentiation program via ERK. We found that ERK induces the expression of ETS factors that mediate transformation into a NSCLC-like state. ATAC-seq demonstrated ERK-driven changes in chromatin accessibility at putative regulatory regions and global chromatin rewiring at neuroendocrine and ETS transcriptional targets. Further, ERK-mediated induction of ETS factors as well as suppression of neuroendocrine differentiation were dependent on histone acetyltransferase activities of CBP/p300. Overall, we describe how the ERK-CBP/p300-ETS axis promotes a lineage shift between neuroendocrine and non-neuroendocrine lung cancer phenotypes and provide rationale for the disruption of this program during transformation-driven resistance to targeted therapy.
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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.