ArticleCell reports2015
Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 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
136 citing papers in PubMed, 250 citations in OpenAlex.
- THBS2: the key hub linking breast cancer stroma, immunity, and therapeutic response.Clinical & experimental metastasis · 2026Review
- Type I interferons induced upon respiratory viral infection impair lung metastatic initiation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting Tumour Heterogeneity through sequential timing of anti-hallmark combination therapies -a hypothesis for implementation.Frontiers in immunology · 2026Review
- Identification, functional insights and therapeutic targeting of EMT tumour states.Nature reviews. Cancer · 2026Review
- THBS2 Promotes Prostate Cancer Malignancy via INHBA-Dependent FAK/PI3K/AKT Signaling Activation.Analytical cellular pathology (Amsterdam) · 2026Article
- Lipocalin-2 in Triple-Negative Breast Cancer: A Review of Its Pathophysiological Role in the Metastatic Cascade.International journal of molecular sciences · 2025Review
- Metal-Organic Frameworks Against Tumor Metastasis: Therapeutic Targets, Strategies, and Challenges for Clinical Translation.Cancer medicine · 2025Review
- PROS1-MERTK Axis Drives Tumor Microenvironment Crosstalk and Progression in Papillary Thyroid Microcarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Integrated mathematical and experimental modeling uncovers enhanced EMT plasticity upon loss of the DLC1 tumor suppressor.PLoS computational biology · 2025Article
- Unveiling the link between chronic inflammation and cancer.Metabolism open · 2025Review
- AXL promotes lymphangiogenesis by amplifying VEGF-C-mediated AKT pathway.Cellular and molecular life sciences : CMLS · 2025Article
- Despicable role of epithelial-mesenchymal transition in breast cancer metastasis: ExhibitingCancer pathogenesis and therapy · 2025Review
- Deciphering molecular pathways driving cancer invasion and metastasis: advances and therapeutic prospects.Frontiers in oncology · 2025Review
- The roles of PD-L1 in the various stages of tumor metastasis.Cancer metastasis reviews · 2024Review
- Integrating bulk RNA-seq and scRNA-seq analyses revealed the function and clinical value of thrombospondins in colon cancer.Computational and structural biotechnology journal · 2024Article
- The complexity of immune evasion mechanisms throughout the metastatic cascade.Nature immunology · 2024Review
- Single-cell analysis of breast cancer metastasis reveals epithelial-mesenchymal plasticity signatures associated with poor outcomes.The Journal of clinical investigation · 2024Article
- The highly metastatic 4T1 breast carcinoma model possesses features of a hybrid epithelial/mesenchymal phenotype.Disease models & mechanisms · 2024Article
- PP2A B55α inhibits epithelial-mesenchymal transition via regulation of Slug expression in non-small cell lung cancer.Cancer letters · 2024Article
- Tumor-Extrinsic Axl Expression Shapes an Inflammatory Microenvironment Independent of Tumor Cell Promoting Axl Signaling in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Article
76 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
During metastatic colonization, tumor cells must establish a favorable microenvironment or niche that will sustain their growth. However, both the temporal and molecular details of this process remain poorly understood. Here, we found that metastatic initiating cells (MICs) exhibit a high capacity for lung fibroblast activation as a result of Thrombospondin 2 (THBS2) expression. Importantly, inhibiting the mesenchymal phenotype of MICs by blocking the epithelial-to-mesenchymal transition (EMT)-associated kinase AXL reduces THBS2 secretion, niche-activating ability, and, consequently, metastatic competence. Subsequently, disseminated metastatic cells revert to an AXL-negative, more epithelial phenotype to proliferate and decrease the phosphorylation levels of TGF-β-dependent SMAD2-3 in favor of BMP/SMAD1-5 signaling. Remarkably, newly activated fibroblasts promote this transition. In summary, our data reveal a crosstalk between cancer cells and their microenvironment whereby the EMT status initially triggers and then is regulated by niche activation during metastatic colonization.
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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.