ArticleGastroenterology2014
Autocrine VEGF signaling promotes proliferation of neoplastic Barrett's epithelial cells through a PLC-dependent pathway.
Article in Gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- A phase II and pharmacodynamic study of sunitinib in relapsed/refractory oesophageal and gastro-oesophageal cancers.British journal of cancer · 2015Trial
- Integrated analysis of single-cell RNA sequencing, transcriptomics, and thermal proteome profiling identifies PLCG1 as the therapeutic target of isopimpinellin in treating rheumatoid arthritis.Cellular & molecular biology letters · 2026Article
- Signaling pathways and targeted interventions for precancers.Signal transduction and targeted therapy · 2026Review
- Predicting Regression of Barrett's Esophagus-Can All the King's Men Put It Together Again?Biomolecules · 2024Article
- Ishophloroglucin A Ameliorates VEGF-Induced Epithelial-Mesenchymal Transition via VEGFR2 Pathway Inhibition in Microgravity-Stimulated Human Retinal Pigment Epithelial Cells.Antioxidants (Basel, Switzerland) · 2022Article
- Metformin Improves Ovarian Cancer Sensitivity to Paclitaxel and Platinum-Based Drugs: A Review of In Vitro Findings.International journal of molecular sciences · 2022Review
- Predictive and Therapeutic Implications of a Novel PLCγ1/SHP2-Driven Mechanism of Cetuximab Resistance in Metastatic Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Gab1 regulates invadopodia and autocrine VEGF through SHP2/ERK1/2 in hilar cholangiocarcinoma cells.American journal of translational research · 2022Article
- Histone Deacetylase Inhibitor I3 Induces the Differentiation of Acute Myeloid Leukemia Cells withJournal of oncology · 2022Article
- Epithelial Stem Cells: Making, Shaping and Breaking the Niche.Advances in experimental medicine and biology · 2022Article
- Itraconazole Exerts Its Antitumor Effect in Esophageal Cancer By Suppressing the HER2/AKT Signaling Pathway.Molecular cancer therapeutics · 2021Article
- Article
- Apatinib regulates the growth of gastric cancer cells by modulating apoptosis and autophagy.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Zinc Gluconate Induces Potentially Cancer Chemopreventive Activity in Barrett's Esophagus: A Phase 1 Pilot Study.Digestive diseases and sciences · 2021Article
- Targeting ERK combined with apatinib may be a promising therapeutic strategy for treating oral squamous cell carcinoma.American journal of cancer research · 2021Article
- Maternal Vit D supplementation in AMA mice and the role of Vit D/VDR signaling in the offspring's cognition.American journal of translational research · 2021Article
- Identification of Unique Transcriptomic Signatures and Hub Genes Through RNA Sequencing and Integrated WGCNA and PPI Network Analysis in Nonerosive Reflux Disease.Journal of inflammation research · 2021Article
- Clinical observation of apatinib-related hypothyroidism in patients with advanced malignancies.Experimental and therapeutic medicine · 2020Article
- VEGF promotes migration and invasion by regulating EMT and MMPs in nasopharyngeal carcinoma.Journal of Cancer · 2020Article
- [Effect of Apatinib on Invasion and Migration of Lung Cancer Cells and Its Mechanism].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2019Article
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsTumor cells express vascular endothelial growth factor (VEGF), which induces angiogenesis. VEGF also activates VEGF receptors (VEGFRs) on or within tumor cells to promote their proliferation in an autocrine fashion. We studied the mechanisms of autocrine VEGF signaling in Barrett's esophagus cells.
methodsUsing Barrett's epithelial cell lines, we measured VEGF and VEGFR messenger RNA and protein, and studied the effects of VEGF signaling on cell proliferation and VEGF secretion. We studied the effects of inhibiting factors in this pathway on levels of phosphorylated phospholipase Cγ1 (PLCG1), protein kinase C, and extracellular signal-regulated kinases (ERK)1/2. We performed immunohistochemical analysis of phosphorylated VEGFR2 on esophageal adenocarcinoma tissues. We studied effects of sunitinib, a VEGFR2 inhibitor, on proliferation of neoplastic cells and growth of xenograft tumors in mice.
resultsNeoplastic and non-neoplastic Barrett's cells expressed VEGF and VEGFR2 messenger RNA and protein, with higher levels in neoplastic cells. Incubation with recombinant human VEGF significantly increased secretion of VEGF protein and cell number; knockdown of PLCG1 markedly reduced the recombinant human VEGF-stimulated increase in levels of phosphorylated PLCG1 and phosphorylated ERK1/2 in neoplastic cells. Esophageal adenocarcinoma tissues showed immunostaining for phosphorylated VEGFR2. Sunitinib inhibited VEGF signaling in neoplastic cells and reduced weight and volume of xenograft tumors in mice.
conclusionsNeoplastic and non-neoplastic Barrett's epithelial cells have autocrine VEGF signaling. In neoplastic Barrett's cells, VEGF activation of VEGFR2 initiates a PLCG1-protein kinase C-ERK pathway that promotes proliferation and is self-sustaining (by causing more VEGF production). Strategies to reduce autocrine VEGF signaling (eg, with sunitinib) might be used to prevent or treat cancer in patients with Barrett's esophagus.
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