ArticleJournal of gastroenterology2026
Formation of the pre-metastatic niche by COL9A1 + cancer-associated fibroblasts via SDC4 engagement promotes multi-organ metastasis in gastric cancer.
Article in Journal of gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetastatic dissemination represents the primary cause of mortality in gastric cancer (GC), with multi-organ involvement posing a formidable therapeutic challenge. While organ-specific adaptations are well-studied, the conserved cellular programs that confer metastatic competence within primary tumors before dissemination remain poorly defined.
methodsWe performed integrated single-cell and spatial transcriptomic profiling on paired primary GC tumors and multi-organ metastases. Computational trajectory inference, regulon analysis, and cell-cell communication networks were employed to delineate metastatic evolution. Functional validation was conducted through in vitro models, including co-culture assays and genetic perturbation.
resultsWe identified a conserved intra-tumoral trajectory from metastasis-initiating cells (MICs) to metastasis-like cells (MLCs) within primary tumors, which transcriptionally converged with cells from anatomically diverse metastases. This progression was orchestrated by an ETS2-centered regulatory network, whose declining activity governed pre-adaptive remodeling. We further resolved cancer-associated fibroblast (CAF) heterogeneity and discovered that ACTA2 + CAFs sustain MIC identity through a specific ligand-receptor interaction, COL9A1-SDC4. Functional assays confirmed that this axis directly drives the migratory and invasive phenotypes of GC cells.
conclusionsThis study reveals that metastatic phenotypes may emerge through transcriptional pre-adaptation within primary gastric tumors, orchestrated by a cell-autonomous ETS2 regulatory network governing trajectory progression and sustained by a specialized ACTA2 + CAF niche that maintains MIC identity via COL9A1-SDC4 signaling. These findings suggest a prevention-focused paradigm, identifying the ETS2 circuit and the COL9A1-SDC4 niche axis as complementary candidate targets for intercepting metastasis at its earliest stage.
Indexed as
Identifiers
41999506What 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.