ArticleOncotarget2017
An oncogenic KRAS transcription program activates the RHOGEF ARHGEF2 to mediate transformed phenotypes in pancreatic cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Biofabrication and artificial intelligence strategies for investigating solid- and fluid-pressure mechanobiology in pancreatic ductal adenocarcinoma.Cancer metastasis reviews · 2026Review
- Early induction of the Rho-GEF ECT2 drives MEK/ERK oncogenic signaling in pancreatic ductal adenocarcinoma.Oncogene · 2026Article
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- Dynamic Coupling of MAPK Signaling to the Guanine Nucleotide Exchange Factor GEF-H1.OncoTargets and therapy · 2025Review
- MiR-4646-5p Acts as a Tumor-Suppressive Factor in Triple Negative Breast Cancer and Targets the Cholesterol Transport Protein GRAMD1B.Non-coding RNA · 2023Article
- High ARHGEF2 (GEF-H1) Expression is Associated with Poor Prognosis Via Cell Cycle Regulation in Patients with Pancreatic Cancer.Annals of surgical oncology · 2021Article
- The Crossroads between RAS and RHO Signaling Pathways in Cellular Transformation, Motility and Contraction.Genes · 2021Review
- Article
- Estrogen Receptor Beta Influences the Inflammatory p65 Cistrome in Colon Cancer Cells.Frontiers in endocrinology · 2021Article
- Haploinsufficiency of RREB1 causes a Noonan-like RASopathy via epigenetic reprogramming of RAS-MAPK pathway genes.Nature communications · 2020Article
- Comparative proteomic analysis uncovers potential biomarkers involved in the anticancer effect of Scutellarein in human gastric cancer cells.Oncology reports · 2020Article
- The Combination of Loss of ALDH1L1 Function and Phenformin Treatment Decreases Tumor Growth inCancers · 2020Article
- Transcription Factor RREB1: from Target Genes towards Biological Functions.International journal of biological sciences · 2020Review
- Co-dependency between KRAS addiction and ARHGEF2 promotes an adaptive escape from MAPK pathway inhibition.Small GTPases · 2019Article
- A family affair: A Ral-exocyst-centered network links Ras, Rac, Rho signaling to control cell migration.Small GTPases · 2019Review
- RAS-Responsive Element-Binding Protein 1 Blocks the Granulocytic Differentiation of Myeloid Leukemia Cells.Oncology research · 2019Article
- Comparative Proteomic Profiling of Tumor-Associated Proteins in Human Gastric Cancer Cells Treated with Pectolinarigenin.Nutrients · 2018Article
- Rho Kinase Inhibition by AT13148 Blocks Pancreatic Ductal Adenocarcinoma Invasion and Tumor Growth.Cancer research · 2018Article
- Wnt5a induces ROR1 to associate with 14-3-3ζ for enhanced chemotaxis and proliferation of chronic lymphocytic leukemia cells.Leukemia · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating mutations of KRAS are nearly ubiquitous in pancreatic adenocarcinomas occurring in greater than 90% of cases. Cellular transformation by oncogenic RAS requires the RHO guanine exchange factor ARHGEF2 (also known as GEF-H1) for tumor growth and survival. Here, we find oncogenic KRAS activates ARHGEF2 through a minimal RAS responsive promoter. We have determined the endogenous ARHGEF2 promoter is positively regulated by the transcription factors ELK1, ETS1, SP1 and SP3 and negatively regulated by the RAS responsive element binding protein (RREB1). We find that the panel of ARHGEF2-regulating transcription factors modulates RAS transformed phenotypes including cellular viability, anchorage-independent growth and invasion-migration of pancreatic cancer cells. RREB1 knockdown activates the amplitude and duration of RHOA via increased ARHGEF2 expression. By relieving the negative regulation of RREB1 on the ARHGEF2 promoter, we determined that ETS1 and SP3 are essential for the normal expression of ARHGEF2 and contribute to the migratory behavior of pancreatic cancer cells. Furthermore, enforced expression of ARHGEF2 rescues loss of SP3 driven invasion-migration and anchorage-independent growth defective phenotypes through restored activation of RHOA. Collectively, our results identify a transcription factor program required for RAS transformation and provide mechanistic insight into the highly metastatic behavior of pancreatic cancer.
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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.