ArticleProceedings of the National Academy of Sciences of the United States of America2023
ERK and c-Myc signaling in host-derived tumor endothelial cells is essential for solid tumor growth.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. 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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Who cites it
25 citing papers in PubMed, 59 citations in OpenAlex.
- Mechanisms of Yiguanjian Decoction against Thyroid Cancer: A Network-Based Pharmacological Investigation.Chinese journal of integrative medicine · 2026Article
- IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review).International journal of molecular medicine · 2026Review
- An RNA-sequencing analysis to determine potential upstream transcriptional regulators of essential amino acid deficiency responses in bovine mammary epithelial cells.BMC genomics · 2026Article
- PTEN Loss Promotes PI3Kβ Phosphorylation and EPHA2/SRC/p-PI3KβY962 Complex Assembly to Drive Tumorigenesis.Cancer discovery · 2026Article
- OGT-Mediated O-GlcNAcylation Stabilizes c-Myc Activity and Promotes Chemoresistance in Triple-Negative Breast Cancer.The breast journal · 2026Article
- GAB2 regulates lipid metabolism by activating the MEK/ERK/c-Myc pathway: impact on renal cell carcinoma progression.European journal of medical research · 2025Article
- Kcnn4/KCa3.1 inhibition blunts polycystic kidney disease progression in mouse models.JCI insight · 2025Article
- STK32C promotes colon tumor progression through activating c-MYC signaling.Cellular and molecular life sciences : CMLS · 2025Article
- ERK pathway reactivation prevents anthrax toxin lethality in mice.Nature microbiology · 2025Article
- L-741626 inhibits hepatocellular carcinoma progression by targeting Ref-1 to suppress MAPK/ERK signalling pathway activity.Biology direct · 2025Article
- ATP depletion in anthrax edema toxin pathogenesis.PLoS pathogens · 2025Article
- Extracellular matrix stiffness regulates the proliferation and migration capacities of lymphatic endothelial cells via FAT1.Frontiers in cell and developmental biology · 2025Article
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- Vilazodone Alleviates Neurogenesis-Induced Anxiety in the Chronic Unpredictable Mild Stress Female Rat Model: Role of Wnt/β-Catenin Signaling.Molecular neurobiology · 2024Article
- A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression.Molecular cancer · 2024Article
- A network pharmacology-based approach to explore the molecular mechanism of Aidi injection against prostate cancer.Heliyon · 2024Article
- Design, Synthesis, and Anti-Leukemic Evaluation of a Series of Dianilinopyrimidines by Regulating the Ras/Raf/MEK/ERK and STAT3/c-Myc Pathways.Molecules (Basel, Switzerland) · 2024Article
- Efficacy of Butyrate to Inhibit Colonic Cancer Cell Growth Is Cell Type-Specific and Apoptosis-Dependent.Nutrients · 2024Article
- Zuojin Pill Alleviates Precancerous Lesions of Gastric Cancer by Modulating the MEK/ERK/c-Myc Pathway: An Integrated Approach of Network Pharmacology, Molecular Dynamics Simulation, and Experimental Validation.Drug design, development and therapy · 2024Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The limited efficacy of the current antitumor microenvironment strategies is due in part to the poor understanding of the roles and relative contributions of the various tumor stromal cells to tumor development. Here, we describe a versatile in vivo anthrax toxin protein delivery system allowing for the unambiguous genetic evaluation of individual tumor stromal elements in cancer. Our reengineered tumor-selective anthrax toxin exhibits potent antiproliferative activity by disrupting ERK signaling in sensitive cells. Since this activity requires the surface expression of the capillary morphogenesis protein-2 (CMG2) toxin receptor, genetic manipulation of CMG2 expression using our cell-type-specific CMG2 transgenic mice allows us to specifically define the role of individual tumor stromal cell types in tumor development. Here, we established mice with CMG2 only expressed in tumor endothelial cells (ECs) and determined the specific contribution of tumor stromal ECs to the toxin's antitumor activity. Our results demonstrate that disruption of ERK signaling only within tumor ECs is sufficient to halt tumor growth. We discovered that c-Myc is a downstream effector of ERK signaling and that the MEK-ERK-c-Myc central metabolic axis in tumor ECs is essential for tumor progression. As such, disruption of ERK-c-Myc signaling in host-derived tumor ECs by our tumor-selective anthrax toxins explains their high efficacy in solid tumor therapy.
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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.