ArticleOncogene2012
Increased vascularity and spontaneous metastasis of breast cancer by hedgehog signaling mediated upregulation of cyr61.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 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.
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Who cites it
77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 116 citations in OpenAlex.
- Signaling Pathways and Natural Compounds in Triple-Negative Breast Cancer Cell Line.Molecules (Basel, Switzerland) · 2022Pooled it
- Genetics of breast cancer bone metastasis: a sequential multistep pattern.Clinical & experimental metastasis · 2014Pooled it
- Traditional Chinese medicine formula Xiang Bei San suppresses the growth and metastasis of breast cancer by regulating macrophage polarization and tumor vascularization.Journal of natural medicines · 2026Article
- Hedgehog signaling pathway is an influential factor on vascular biology: a review.Journal of physiology and biochemistry · 2025Review
- Review
- Probing the biological efficacy and mechanistic pathways of natural compounds in breast cancer therapy via the Hedgehog signaling pathway.Journal of pharmaceutical analysis · 2025Review
- Brd7 loss reawakens dormant metastasis initiating cells in lung by forging an immunosuppressive niche.Nature communications · 2025Article
- Interactions between hedgehog signaling pathway and the complex tumor microenvironment in breast cancer: current knowledge and therapeutic promises.Cell communication and signaling : CCS · 2024Review
- Alterations of ceramide synthesis induce PD-L1 internalization and signaling to regulate tumor metastasis and immunotherapy response.Cell reports · 2024Article
- The regulation of microRNAs on chemoresistance in triple-negative breast cancer: a recent update.Epigenomics · 2024Review
- Involvement of redox signalling in tumour cell dormancy and metastasis.Cancer metastasis reviews · 2023Review
- Advances with metal oxide-based nanoparticles as MDR metastatic breast cancer therapeutics and diagnostics.RSC advances · 2022Review
- Higher Expressions of SHH and AR Are Associated with a Positive Receptor Status and Have Impact on Survival in a Cohort of Croatian Breast Cancer Patients.Life (Basel, Switzerland) · 2022Article
- Molecular Mechanisms, Biomarkers and Emerging Therapies for Chemotherapy Resistant TNBC.International journal of molecular sciences · 2022Review
- Quantitative Longitudinal Imaging Reveals that Inhibiting Hedgehog Activity Alleviates the Hypoxic Tumor Landscape.Molecular cancer research : MCR · 2022Article
- Molecular targets and therapeutics in chemoresistance of triple-negative breast cancer.Medical oncology (Northwood, London, England) · 2021Review
- miR‑367‑3p downregulates Rab23 expression and inhibits Hedgehog signaling resulting in the inhibition of the proliferation, migration, and invasion of prostate cancer cells.Oncology reports · 2021Article
- Physalin A, 13,14-Seco-16, 24-Cyclo-Steroid, Inhibits Stemness of Breast Cancer Cells by Regulation of Hedgehog Signaling Pathway and Yes-Associated Protein 1 (YAP1).International journal of molecular sciences · 2021Article
- Differential Expression ofCancers · 2021Article
- Hedgehog Signaling: Implications in Cancers and Viral Infections.International journal of molecular sciences · 2021Review
17 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
5 authors at 2 institutions in 1 country.
Funding
Abstract
The Hedgehog (Hh) pathway is well known for its involvement in angiogenesis and vasculogenesis during ontogeny. The ligand, Sonic Hh (SHH), has an important role in vascular formation during development. However, SHH expression is upregulated on tumor cells and can impact the tumor microenvironment. We have investigated the effects of autocrine as well as paracrine Hh signaling on tumor cells as well as on endothelial cells, respectively. Upon constitutive expression of SHH, breast cancer cells showed aggressive behavior and rapid xenograft growth characterized by highly angiogenic tumors that were spontaneously metastatic. In these cells, SHH caused activation of the Hh transcription factor, GLI1, leading to upregulated expression of the potent pro-angiogenic secreted molecule, CYR61 (cysteine-rich angiogenic inducer 61). Silencing of CYR61 from these SHH-expressing Hh activated cells blunted the malignant behavior of the tumor cells and resulted in reduced tumor vasculature and limited hematogenous metastases. Thus, CYR61 is a critical downstream contributor to the Hh influenced pro-angiogenic tumor microenvironment. We also observed concomitant upregulation of SHH and CYR61 transcripts in tumors from patients with advanced breast cancer, further ratifying the clinical relevance of our findings. In summary, we have defined a novel, VEGF-independent, clinically relevant, pro-angiogenic factor, CYR61, that is a transcriptional target of Hh-GLI signaling.
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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.