ArticleNature cell biology2015
RasGRP1 opposes proliferative EGFR-SOS1-Ras signals and restricts intestinal epithelial cell growth.
Article in Nature cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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.
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.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Article
- Article
- Rasgrp1-Mediated Dampening of EGFR Signals Supports Coordinated Mammary Gland Development.Cells · 2026Article
- Small vesicles, big potential: A review of innovative exosome delivery and molecular mechanisms in preclinical myocardial infarction models.Animal models and experimental medicine · 2026Review
- Cell-type-resolved genetic regulatory variation shapes inflammatory bowel disease risk.medRxiv : the preprint server for health sciences · 2025Article
- Co-targeting SOS1 enhances the antitumor effects of KRASNature cancer · 2024Article
- Phosphorylation of RasGRP1 by Shc3 prevents RasGRP1 degradation and contributes to Ras/c-Jun activation in hepatocellular carcinoma.Molecular and cellular biochemistry · 2024Article
- Targeting guanine nucleotide exchange factors for novel cancer drug discovery.Expert opinion on drug discovery · 2024Review
- Article
- SOS2 modulates the threshold of EGFR signaling to regulate osimertinib efficacy and resistance in lung adenocarcinoma.Molecular oncology · 2024Article
- Exploring the multifaceted role of RASGRP1 in disease: immune, neural, metabolic, and oncogenic perspectives.Cell cycle (Georgetown, Tex.) · 2024Review
- Development of PROTACS degrading KRAS and SOS1.Oncology research · 2024Review
- Comprehensive analysis of bulk and single-cell RNA sequencing data reveals Schlafen-5 (SLFN5) as a novel prognosis and immunity.International journal of medical sciences · 2024Article
- Transcriptional-translational conflict is a barrier to cellular transformation and cancer progression.Cancer cell · 2023Article
- A Focused Review of Ras Guanine Nucleotide-Releasing Protein 1 in Immune Cells and Cancer.International journal of molecular sciences · 2023Review
- Development of SOS1 Inhibitor-Based Degraders to TargetJournal of medicinal chemistry · 2022Article
- RasGRP1 promotes the acute inflammatory response and restricts inflammation-associated cancer cell growth.Nature communications · 2022Article
- Immune cells-derived exosomes function as a double-edged sword: role in disease progression and their therapeutic applications.Biomarker research · 2022Review
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- circPTEN suppresses colorectal cancer progression through regulating PTEN/AKT pathway.Molecular therapy. Nucleic acids · 2021Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The character of EGFR signals can influence cell fate but mechanistic insights into intestinal EGFR-Ras signalling are limited. Here we show that two distinct Ras nucleotide exchange factors, RasGRP1 and SOS1, lie downstream of EGFR but act in functional opposition. RasGRP1 is expressed in intestinal crypts where it restricts epithelial growth. High RasGRP1 expression in colorectal cancer (CRC) patient samples correlates with a better clinical outcome. Biochemically, we find that RasGRP1 creates a negative feedback loop that limits proliferative EGFR-SOS1-Ras signals in CRC cells. Genetic Rasgrp1 depletion from mice with either an activating mutation in KRas or with aberrant Wnt signalling due to a mutation in Apc resulted in both cases in exacerbated Ras-ERK signalling and cell proliferation. The unexpected opposing cell biological effects of EGFR-RasGRP1 and EGFR-SOS1 signals in the same cell shed light on the intricacy of EGFR-Ras signalling in normal epithelium and carcinoma.
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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.