ArticleNature medicine2017
KLF4-dependent perivascular cell plasticity mediates pre-metastatic niche formation and metastasis.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 1 of them a synthesis that pooled it.
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.
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
163 citing papers in PubMed, 1 synthesis or guideline pooled it, 286 citations in OpenAlex.
- Pericyte in Oral Squamous Cell Carcinoma: A Systematic Review.Head and neck pathology · 2020Pooled it
- Extracellular Matrix Remodeling in Tumors: Forces Beyond Fibroblasts.Cancer research · 2026Article
- Vascular Smooth Muscle Cell Plasticity in Atherosclerosis: Mechanisms, Recent Advances, and Therapeutic Implications.Reviews in cardiovascular medicine · 2026Review
- Targeting FAPActa pharmaceutica Sinica. B · 2026Article
- Mechanisms of Pericyte-Mediated Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The vascular niche: an orchestrator of the spatiotemporal dynamics of distant metastasis.Acta pharmacologica Sinica · 2026Review
- Cancer-associated fibroblasts as key regulators of lipid metabolism in the tumour microenvironment.Oncogene · 2026Review
- The pre-metastatic niche: mechanisms, heterogeneity, and therapeutic opportunities.Molecular cancer · 2026Review
- Article
- Stromal cells contribute to progression, recurrence, and metastasis in oral squamous cell carcinoma: a call for therapy.Journal of translational medicine · 2026Review
- Krüppel-Like Factor 4, a Hub Gate for Cell Crosstalk in Tumor Microenvironment.Cancer medicine · 2026Review
- Metabolic adaptations in cancer progression.Physiological reviews · 2026Review
- Orchestrating the pre-metastatic niche: roles of stromal mediators and immune cells in metastatic progression and therapeutic targeting.Frontiers in immunology · 2026Review
- Tumor-Associated Pericytes: Tumorigenicity and Targeting for Cancer Therapy.Current vascular pharmacology · 2026Review
- Emerging role of cancer-associated fibroblasts in the premetastatic niche.Molecular cancer · 2025Review
- KLF4 in cancer chemoresistance: molecular mechanisms and therapeutic implications.Discover oncology · 2025Review
- Plasticity and Functional Heterogeneity of Cancer-Associated Fibroblasts.Cancer research · 2025Review
- Lung metastases.Nature reviews. Disease primers · 2025Review
- Pericytes in hematogenous metastasis: mechanistic insights and therapeutic approaches.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Spatial Omics Profiling of Treatment-Naïve Lung Adenocarcinoma with Brain Metastasis as the Initial Presentation.Cancers · 2025Article
103 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
A deeper understanding of the metastatic process is required for the development of new therapies that improve patient survival. Metastatic tumor cell growth and survival in distant organs is facilitated by the formation of a pre-metastatic niche that is composed of hematopoietic cells, stromal cells and extracellular matrix (ECM). Perivascular cells, including vascular smooth muscle cells (vSMCs) and pericytes, are involved in new vessel formation and in promoting stem cell maintenance and proliferation. Given the well-described plasticity of perivascular cells, we hypothesized that perivascular cells similarly regulate tumor cell fate at metastatic sites. We used perivascular-cell-specific and pericyte-specific lineage-tracing models to trace the fate of perivascular cells in the pre-metastatic and metastatic microenvironments. We show that perivascular cells lose the expression of traditional vSMC and pericyte markers in response to tumor-secreted factors and exhibit increased proliferation, migration and ECM synthesis. Increased expression of the pluripotency gene Klf4 in these phenotypically switched perivascular cells promoted a less differentiated state, characterized by enhanced ECM production, that established a pro-metastatic fibronectin-rich environment. Genetic inactivation of Klf4 in perivascular cells decreased formation of a pre-metastatic niche and metastasis. Our data revealed a previously unidentified role for perivascular cells in pre-metastatic niche formation and uncovered novel strategies for limiting 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.