ArticleMolecular cancer2026
A paracrine-to-autocrine shunt of GREM1 fuels colorectal cancer metastasis via ACVR1C.
Article in Molecular cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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
2 citing papers in PubMed.
- Fibroblast-derived gremlin-1 Is associated with ovarian cancer-cell phenotypes in co-culture models.Frontiers in oncology · 2026Article
- Profibrogenic Gremlin-1 expression in prostate cancer and the clinicopathologic association.Frontiers in oncology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors.
Funding
Abstract
backgroundTumor cells typically rely on paracrine stromal signals to guide malignant behavior, yet whether they gain signaling autonomy and thereby reduce microenvironment dependency during metastasis remains unclear.
methodsGremlin 1 (GREM1) and activin A receptor type 1C (ACVR1C) expression levels and cellular distribution were analyzed by immunohistochemistry, immunofluorescence (IF) staining, and single-cell transcriptomics in colorectal cancer (CRC) specimens across stages I-IV. The GREM1-ACVR1C interaction was identified and validated by interaction proteomics, co-immunoprecipitation, IF, and microscale thermophoresis (MST). Functional roles of the GREM1-ACVR1C axis in epithelial-mesenchymal transition (EMT) and metastasis were examined by transcriptomic profiling, pathway analysis, immunoblotting, reverse transcription quantitative PCR (RT-qPCR), scratch and transwell assays, and genetically engineered and xenograft mouse models. An inhibitory peptide targeting the GREM1-ACVR1C interface was designed and evaluated.
resultsWhile GREM1 remains restricted to stromal cells in earlier-stage (I-III) CRC, its ectopic expression in tumor epithelium increases markedly in stage IV. Mechanistically, we identify ACVR1C as a direct, high-affinity epithelial receptor for GREM1. Their interaction, independent of canonical transforming growth factor β receptor (TGFβR) and bone morphogenetic protein (BMP) signaling, activates SMAD2/3, which in turn induces the transcription of SNAI1 and GREM1, thereby establishing a self-sustaining autocrine loop that amplifies EMT. Disrupting this loop via stromal GREM1 deletion, epithelial ACVR1C knockdown, kinase inhibition, or a novel GREM1-blocking peptide targeting the GREM1-ACVR1C binding interface significantly impairs CRC metastasis in vivo. Remarkably, while stromal GREM1 is required to initiate this loop, epithelial-derived GREM1 is sufficient to maintain metastatic progression. Clinically, epithelial GREM1 or ACVR1C expression predicts aggressive disease and poor survival.
conclusionsOur findings define a paradigm wherein CRC cells hijack the stromal factor GREM1 to establish a tumor-autonomous GREM1-ACVR1C autocrine loop. This loop licenses signaling independence, drives sustained EMT, and represents a novel, actionable vulnerability in advanced CRC.
Indexed as
Identifiers
What Socratic 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 Socratic graph.