ArticleOncogene2008
Constitutive activation of the Raf-MAPK pathway causes negative feedback inhibition of Ras-PI3K-AKT and cellular arrest through the EphA2 receptor.
Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 104 citations in OpenAlex.
- Cetuximab co-treatment with KRAS G12C inhibitors fulzerasib and sotorasib in human KRAS G12C non-small cell lung cancer cells.Cell death discovery · 2026Article
- Exogenous ephrin-A3 reverses loss of vaginal epithelial barrier protection in progestin-treated mice.Mucosal immunology · 2025Article
- Association of Single-Nucleotide Polymorphisms onInternational journal of molecular sciences · 2025Article
- Fibronectin-dependent integrin signaling drives EphA2 expression in vascular smooth muscle cells.American journal of physiology. Cell physiology · 2025Article
- Intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase-dependent mechanism.eLife · 2024Article
- Multi-layered proteomics identifies insulin-induced upregulation of the EphA2 receptor via the ERK pathway which is dependent on low IGF1R level.Scientific reports · 2024Article
- Master regulators of neurogenesis: the dynamic roles of Ephrin receptors across diverse cellular niches.Translational psychiatry · 2024Review
- Review
- Nucleoli and the nucleoli-centromere association are dynamic during normal development and in cancer.Molecular biology of the cell · 2023Article
- Eph Receptors in Cancer.Biomedicines · 2023Review
- The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products.Antioxidants (Basel, Switzerland) · 2022Review
- NADPH oxidase 4 signaling in a ventilator-induced lung injury mouse model.Respiratory research · 2022Article
- Ligands with different dimeric configurations potently activate the EphA2 receptor and reveal its potential for biased signaling.iScience · 2022Article
- Proximity Tagging Identifies the Glycan-Mediated Glycoprotein Interactors of Galectin-1 in Muscle Stem Cells.ACS chemical biology · 2021Article
- MEK inhibition overcomes resistance to EphA2-targeted therapy in uterine cancer.Gynecologic oncology · 2021Article
- EphA2 and EGFR: Friends in Life, Partners in Crime. Can EphA2 Be a Predictive Biomarker of Response to Anti-EGFR Agents?Cancers · 2021Review
- Effect of EphA2 knockdown on melanoma metastasis depends on intrinsic ephrinA1 level.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Sex Differences in Neuroplasticity- and Stress-Related Gene Expression and Protein Levels in the Rat Hippocampus Following Oxycodone Conditioned Place Preference.Neuroscience · 2019Article
- Interaction between p53 and Ras signaling controls cisplatin resistance via HDAC4- and HIF-1α-mediated regulation of apoptosis and autophagy.Theranostics · 2019Article
- HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance.Endocrine connections · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
The Raf-mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinase (PI3K)-AKT pathways are two downstream effectors of the small GTPase Ras. Although both pathways are positively regulated by Ras, the Raf-MAPK and PI3K-AKT pathways have been shown to control opposing functions within the cell, suggesting a need for cross-talk regulation. The PI3K-AKT pathway can inhibit the Raf-MAPK pathway directly during processes such as muscle differentiation. Here we describe the ability of the Raf-MAPK pathway to negatively regulate the PI3K-AKT pathway during cellular arrest. Constitutive activation of Raf or methyl ethyl ketone 1 (MEK1) leads to inhibition of AKT and cellular arrest. Furthermore, we show that activation of Raf-MEK1 signaling causes negative feedback inhibition of Ras through the ephrin receptor EphA2. EphA2-mediated negative feedback inhibition is required for Raf-induced AKT inhibition and cell cycle arrest, therefore establishing the inhibition of the Ras-PI3K-AKT pathway as a necessary event for the Raf-MEK1-regulated cellular arrest.
Indexed as
Identifiers
What OpenQuestion holds
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.