ArticlePloS one2012
GEP100/Arf6 is required for epidermal growth factor-induced ERK/Rac1 signaling and cell migration in human hepatoma HepG2 cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 53 citations in OpenAlex.
- Akt-elicited phosphorylation of Acapin steers cell migration.Journal of molecular cell biology · 2025Article
- ARF6 as a Novel Activator of HIF-2α in Pulmonary Arterial Hypertension.American journal of respiratory cell and molecular biology · 2025Article
- ARF6 promotes hepatocellular carcinoma proliferation through activating STAT3 signaling.Cancer cell international · 2023Article
- Prognostic impact of MICALL1 and associates with immune infiltration in liver hepatocellular carcinoma patients.Cancer biomarkers : section A of Disease markers · 2023Article
- Physiological and Pathological Roles of the Cytohesin Family in Neurons.International journal of molecular sciences · 2022Review
- miR-28-3p inhibits prostate cancer cell proliferation, migration and invasion, and promotes apoptosis by targeting ARF6.Experimental and therapeutic medicine · 2021Article
- Arf6-driven endocytic recycling of CD147 determines HCC malignant phenotypes.Journal of experimental & clinical cancer research : CR · 2019Article
- Knockdown of Arf6 increases drug sensitivity and inhibits proliferation, migration and invasion in gastric cancer SGC-7901 cells.Oncology letters · 2018Article
- Article
- Arf proteins in cancer cell migration.Small GTPases · 2016Review
- Ral-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling.Cellular signalling · 2016Article
- ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma.Cancer cell · 2016Article
- Type II cyclic guanosine monophosphate-dependent protein kinase inhibits Rac1 activation in gastric cancer cells.Oncology letters · 2015Article
- Modulation of Regorafenib effects on HCC cell lines by epidermal growth factor.Cancer chemotherapy and pharmacology · 2015Article
- EGF-reduced Wnt5a transcription induces epithelial-mesenchymal transition via Arf6-ERK signaling in gastric cancer cells.Oncotarget · 2015Article
- Arf6 regulates EGF-induced internalization of E-cadherin in breast cancer cells.Cancer cell international · 2015Article
- The Role of ARF6 in Biliary Atresia.PloS one · 2015Article
- bFGF Promotes the Migration of Human Dermal Fibroblasts under Diabetic Conditions through Reactive Oxygen Species Production via the PI3K/Akt-Rac1- JNK Pathways.International journal of biological sciences · 2015Article
- Article
- Effects of Arf6 downregulation on biological characteristics of human prostate cancer cells.International braz j urol : official journal of the Brazilian Society of UrologyArticle
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEpidermal growth factor (EGF) signaling is implicated in the invasion and metastasis of hepatoma cells. However, the signaling pathways for EGF-induced motility of hepatoma cells remain undefined. METHODOLOGY/PRINCIPAL
findingsWe found that EGF dose-dependently stimulated the migration of human hepatoma cells HepG2, with the maximal effect at 10 ng/mL. Additionally, EGF increased Arf6 activity, and ectopic expression of Arf6 T27N, a dominant negative Arf6 mutant, largely abolish EGF-induced cell migration. Blocking GEP100 with GEP100 siRNA or GEP100-△PH, a pleckstrin homology (PH) domain deletion mutant of GEP100, blocked EGF-induced Arf6 activity and cell migration. EGF also increased ERK and Rac1 activity. Ectopic expression GEP100 siRNA, GEP100-△PH, or Arf6-T27N suppressed EGF-induced ERK and Rac1 activity. Furthermore, blocking ERK signaling with its inhibitor U0126 remarkably inhibited both EGF-induced Rac1 activation as well as cell migration, and ectopic expression of inactive mutant form of Rac1 (Rac1-T17N) also largely abolished EGF-induced cell migration. CONCLUSIONS/SIGNIFICANCE: Taken together, this study highlights the function of the PH domain of GEP100 and its regulated Arf6/ERK/Rac1 signaling cascade in EGF-induced hepatoma cell migration. These findings could provide a rationale for designing new therapy based on inhibition of hepatoma metastasis.
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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.