ArticleOncogene2020
Bidirectional tumor/stroma crosstalk promotes metastasis in mesenchymal colorectal cancer.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
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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.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Targeting fibroblast TXNDC5 resolves tumor desmoplasia and PD-1 resistance in colorectal cancer with mesenchymal traits.Nature communications · 2026Article
- Advances in targeting cancer-associated fibroblasts through single-cell spatial transcriptomic sequencing.Biomarker research · 2024Review
- Periostin-TGF-β feedforward loop contributes to tumour-stroma crosstalk in liver metastatic outgrowth of colorectal cancer.British journal of cancer · 2024Article
- Nanomedicine Strategies for Targeting Tumor Stroma.Cancers · 2023Review
- How the interplay among the tumor microenvironment and the gut microbiota influences the stemness of colorectal cancer cells.World journal of stem cells · 2023Review
- TGF-β Signaling in Metastatic Colorectal Cancer (mCRC): From Underlying Mechanism to Potential Applications in Clinical Development.International journal of molecular sciences · 2022Review
- Selective targeting BMP2 and 4 in SMAD4 negative esophageal adenocarcinoma inhibits tumor growth and aggressiveness in preclinical models.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Tumor budding and fibrotic focus-proposed grading system for tumor budding in invasive carcinoma no special type of the breast.Virchows Archiv : an international journal of pathology · 2022Article
- CCL7 and TGF-β secreted by MSCs play opposite roles in regulating CRC metastasis in a KLF5/CXCL5-dependent manner.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Review
- Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years.Frontiers in cell and developmental biology · 2022Review
- Tumour heterogeneity and evolutionary dynamics in colorectal cancer.Oncogenesis · 2021Review
- Liver Immune Microenvironment and Metastasis from Colorectal Cancer-Pathogenesis and Therapeutic Perspectives.Cancers · 2021Review
- Regulation of Cancer Metastasis by TRAIL/Death Receptor Signaling.Biomolecules · 2021Review
- Fibroblast Subsets in Intestinal Homeostasis, Carcinogenesis, Tumor Progression, and Metastasis.Cancers · 2021Review
- Development and Validation of an Autophagy-Stroma-Based Microenvironment Gene Signature for Risk Stratification in Colorectal Cancer.OncoTargets and therapy · 2021Article
- Extracellular BMP Antagonists, Multifaceted Orchestrators in the Tumor and Its Microenvironment.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with the mesenchymal subtype colorectal cancer (CRC) have a poor prognosis, in particular patients with stroma-rich tumors and aberrant SMAD4 expression. We hypothesized that interactions between SMAD4-deficient CRC cells and cancer-associated fibroblasts provide a biological explanation. In transwell invasion assays, fibroblasts increased the invasive capacity of SMAD4-deficient HT29 CRC cells, but not isogenic SMAD4-proficient HT29 cells. A TGF-β/BMP-specific array showed BMP2 upregulation by fibroblasts upon stimulation with conditioned medium from SMAD4-deficient CRC cells, while also stimulating their invasion. In a mouse model for experimental liver metastasis, the co-injection of fibroblasts increased metastasis formation of SMAD4-deficient CRC cells (p = 0.02) but not that of SMAD4-proficient CRC cells. Significantly less metastases were seen in mice co-injected with BMP2 knocked-down fibroblasts. Fibroblast BMP2 expression seemed to be regulated by TRAIL, a factor overexpressed in SMAD4-deficient CRC cells. In a cohort of 146 stage III CRC patients, we showed that patients with a combination of high stromal BMP2 expression and the loss of tumor SMAD4 expression had a significantly poorer overall survival (HR 2.88, p = 0.04). Our results suggest the existence of a reciprocal loop in which TRAIL from SMAD4-deficient CRC cells induces BMP2 in fibroblasts, which enhances CRC invasiveness and metastasis.
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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.