ArticleThe Journal of clinical investigation2012
SIX1 induces lymphangiogenesis and metastasis via upregulation of VEGF-C in mouse models of breast cancer.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 2 of them syntheses 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
78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 118 citations in OpenAlex.
- The Significance of SIX1 as a Prognostic Biomarker for Survival Outcome in Various Cancer Patients: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2021Pooled it
- Pooled it
- Six1 haploinsufficiency is associated with activation of NF-κB and TNF-related transcriptional signatures in aging mice.Cell death & disease · 2026Article
- Lymphatic Endothelial Cells and Organ-Associated Lymphangiogenesis in Tumor Microenvironment.Cells · 2025Review
- Effects of Thymidine Phosphorylase and Sine Oculis Homeobox Homologue 1 on the Prognosis and Immune Microenvironment of Gastric Cancer.Current medical science · 2025Article
- SIX1 aggravates the progression of spinal cord injury in mice by promoting M1 polarization of microglia.Scientific reports · 2025Article
- The Ku70-SIX1-GPT2 axis regulates alpha-ketoglutarate metabolism to drive progression of prostate cancer.Oncogene · 2025Article
- Phosphorylation determines the glucose metabolism reprogramming and tumor-promoting activity of sine oculis homeobox 1.Signal transduction and targeted therapy · 2024Article
- Transcriptional Regulation of De Novo Lipogenesis by SIX1 in Liver Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Cytoplasmatic Localization of Six1 in Male Testis and Spermatogonial Stem Cells.International journal of stem cells · 2024Article
- Biochemical characterization of the Eya and PP2A-B55α interaction.The Journal of biological chemistry · 2024Article
- Targeting sine oculis homeoprotein 1 (SIX1): A review of oncogenic roles and potential natural product therapeutics.Heliyon · 2024Review
- In Vitro Phosphatase Assays for the Eya2 Tyrosine Phosphatase.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Adipose Mesenchymal Stem Cell-derived Exosomes Enhanced Glycolysis through the SIX1/HBO1 Pathway against Oxygen and Glucose Deprivation Injury in Human Umbilical Vein Endothelial Cells.Current stem cell research & therapy · 2024Article
- SIX1 amplification modulates stemness and tumorigenesis in breast cancer.Journal of translational medicine · 2023Article
- SIX1 and EWS/FLI1 co-regulate an anti-metastatic gene network in Ewing Sarcoma.Nature communications · 2023Article
- Retinal determination gene networks: from biological functions to therapeutic strategies.Biomarker research · 2023Review
- Both a hypoxia-inducible EYA3 and a histone acetyltransferase p300 function as coactivators of SIX5 to mediate tumorigenesis and cancer progression.Annals of translational medicine · 2022Article
- Article
- Opposing Roles of Vascular Endothelial Growth Factor C in Metastatic Dissemination and Resistance to Radio/Chemotherapy: Discussion of Mechanisms and Therapeutic Strategies.Methods in molecular biology (Clifton, N.J.) · 2022Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
An association between lymph node metastasis and poor prognosis in breast cancer was observed decades ago. However, the mechanisms by which tumor cells infiltrate the lymphatic system are not completely understood. Recently, it has been proposed that the lymphatic system has an active role in metastatic dissemination and that tumor-secreted growth factors stimulate lymphangiogenesis. We therefore investigated whether SIX1, a homeodomain-containing transcription factor previously associated in breast cancer with lymph node positivity, was involved in lymphangiogenesis and lymphatic metastasis. In a model in which human breast cancer cells were injected into immune-compromised mice, we found that SIX1 expression promoted peritumoral and intratumoral lymphangiogenesis, lymphatic invasion, and distant metastasis of breast cancer cells. SIX1 induced transcription of the prolymphangiogenic factor VEGF-C, and this was required for lymphangiogenesis and lymphatic metastasis. Using a mouse mammary carcinoma model, we found that VEGF-C was not sufficient to mediate all the metastatic effects of SIX1, indicating that SIX1 acts through additional, VEGF-C-independent pathways. Finally, we verified the clinical significance of this prometastatic SIX1/VEGF-C axis by demonstrating coexpression of SIX1 and VEGF-C in human breast cancer. These data define a critical role for SIX1 in lymphatic dissemination of breast cancer cells, providing a direct mechanistic explanation for how VEGF-C expression is upregulated in breast cancer, resulting in lymphangiogenesis and metastasis.
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What 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.