ArticleJournal of cancer research and clinical oncology2018
Cancer-associated fibroblasts promote gastric tumorigenesis through EphA2 activation in a ligand-independent manner.
Article in Journal of cancer research and clinical oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 41 citations in OpenAlex.
- Article
- Mechanism of crosstalk between Helicobacter pylori and immune stromal cells in the development and occurrence of gastric cancer.Discover oncology · 2025Review
- Role and value of the tumor microenvironment in the progression and treatment resistance of gastric cancer (Review).Oncology reports · 2025Review
- Exploration of the shared pathways and common biomarkers in cervical and ovarian cancer using integrated bioinformatics analysis.Discover oncology · 2024Article
- Article
- Erythropoietin-induced hepatocyte receptor A2 regulates effect of pyroptosis on gastrointestinal colorectal cancer occurrence and metastasis resistance.World journal of gastrointestinal oncology · 2024Review
- Targeting the EphA2 pathway: could it be the way for bone sarcomas?Cell communication and signaling : CCS · 2024Review
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Targeting Host Tyrosine Kinase Receptor EPHA2 Signaling Affects Uropathogen Infection in Human Bladder Epithelial Cells.Pathogens (Basel, Switzerland) · 2022Article
- Review
- EPHA2, EPHA4, and EPHA6 Expression in Uveal Melanomas: Searching for the Culprits of Neoplasia.Diagnostics (Basel, Switzerland) · 2022Article
- ALW-II-41-27, an EphA2 inhibitor, inhibits proliferation, migration and invasion of cervical cancer cells via inhibition of the RhoA/ROCK pathway.Oncology letters · 2022Article
- An integrated analysis of single-cell and bulk transcriptomics reveals EFNA1 as a novel prognostic biomarker for cervical cancer.Human cell · 2022Article
- GLIS1 in Cancer-Associated Fibroblasts Regulates the Migration and Invasion of Ovarian Cancer Cells.International journal of molecular sciences · 2022Article
- Tyrosine Phosphorylation Profiling Revealed the Signaling Network Characteristics of CAMKK2 in Gastric Adenocarcinoma.Frontiers in genetics · 2022Article
- Extracellular Vesicles Promote the Formation of Pre-Metastasis Niche in Gastric Cancer.Frontiers in immunology · 2022Review
- The Pan-Cancer Crosstalk Between theFrontiers in cell and developmental biology · 2022Article
- Eliciting an immune-mediated antitumor response through oncolytic herpes simplex virus-based shared antigen expression in tumors resistant to viroimmunotherapy.Journal for immunotherapy of cancer · 2021Article
- EphA2 signaling within integrin adhesions regulates fibrillar adhesion elongation and fibronectin deposition.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- The Clinical Impact of the EPH/Ephrin System in Cancer: Unwinding the Thread.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeUnder physiologic conditions, the binding of erythropoietin-producing hepatocellular (Eph) A2 receptor and its ligand ephrinA1 results in decreased EphA2 level and tumor suppression. However, EphA2 and ephrinA1 are highly expressed in human cancers including gastric adenocarcinoma. In this study, we tested our hypothesis that cancer-associated fibroblasts (CAFs) promote gastric tumorigenesis through EphA2 signaling in a ligand-independent manner.
methodsExpression of EphA2 protein in primary tumor tissues of 91 patients who underwent curative surgery for gastric adenocarcinoma was evaluated by immunohistochemistry and western blotting. Conditioned medium of cancer-associated fibroblasts (CAF-CM) was used to evaluate the tumorigenic effect of CAFs on gastric cancer cell lines. Epithelial-mesenchymal transition (EMT), cell proliferation, migration, and invasion were assessed. EphrinA1-Fc ligand was used to determine the suppressor role of EphA2 receptor-ligand binding.
resultsCAF-CM-induced EMT and promoted cancer cell motility even without cell-cell interaction. Treatment with a selective EphA2 inhibitor (ALW-II-41-27) or EphA2-targeted siRNA markedly reduced CAF-CM-induced gastric tumorigenesis. EphrinA1-Fc ligand treatment showing ligand-dependent tumor suppression diminished the EphA2 expression and EMT progression. In contrast, ephrinA1-targeted siRNA did not significantly affect CAF-CM-mediated increases in EphA2 expression and EMT progression. Treatment with VEGF showed effects like CAF-CM in terms of EphA2 activation and EMT progression.
conclusionCAFs may contribute to gastric tumorigenesis by activating EphA2 signaling pathway in a ligand-independent manner. Our results suggest that ligand-independent activation of EphA2 was triggered by VEGF released from CAF-CM. Our result may partially explain why ligand-dependent tumor suppressor roles of EphA2 are not evident in gastric cancer despite the prominent level of ephrinA1.
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.