ArticleOncogene2021
VEGF-C mediates tumor growth and metastasis through promoting EMT-epithelial breast cancer cell crosstalk.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed.
- Epithelial-Mesenchymal Transition, Immune Response, and Extracellular Matrix Remodelling in Oral Cancer.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026Article
- Single-cell and spatial transcriptomic analysis reveals PAX5's role and regulatory mechanisms in gastric adenocarcinoma lymph node metastasis.Journal of translational medicine · 2026Article
- [Research on tissue regeneration and engineered scaffold materials in prevention and treatment of lymphedema].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Review
- Glutathione responsive iNOS inhibiting polymeric prodrug for targeted Inhibition of angiogenesis.Journal of nanobiotechnology · 2026Article
- Thrombospondin-4 drives lymphangiogenesis through cooperation with VEGF-C in human bladder cancer.International journal of medical sciences · 2026Article
- β-Lapachone sensitizes glioblastoma to Temozolomide by inhibiting NF-κB signaling.Functional & integrative genomics · 2025Article
- Gradient perfusion features can effectively identify sentinel lymph node metastasis in early breast cancer.BMC cancer · 2025Article
- Prediction of regional lymph node metastasis in rectal cancer: a novel model based on transrectal contrast-enhanced ultrasound.Discover oncology · 2025Article
- SIX1 transmits signals for breast cancer progression via the ZEB1/IL6/STAT3 signaling axis.Oncogene · 2025Article
- Article
- Masters of adaptation: How cancer and immune cell plasticity mediates tumor progression.PLoS biology · 2025Review
- Regulatory effects of lncRNA PVT1 on transcriptome in human breast cancer MDA-MB-231 cell line determined by in silico analyses.Chromosoma · 2025Article
- GLI2 Facilitates Tumor Immune Evasion and Immunotherapeutic Resistance by Coordinating WNT and Prostaglandin Signaling.Cancer research · 2025Article
- Comparative impact of proton versus photon irradiation on triple-negative breast cancer: Role of VEGFC in tumour aggressiveness.Clinical and translational medicine · 2025Article
- Alda‑1 restores ALDH2‑mediated alcohol metabolism to inhibit the NF‑κB/VEGFC axis in head and neck cancer.International journal of molecular medicine · 2025Article
- Tissue-Engineered Therapeutics for Lymphatic Regeneration: Solutions for Myocardial Infarction and Secondary Lymphedema.Advanced healthcare materials · 2025Review
- Epigenome and three-dimensional genome architecture remodeling during NDM29-mediated retro-transformation of neuroblastoma cells.PloS one · 2025Article
- Role of transforming growth factor-β1 pathway in angiogenesis induced by chronic stress in colorectal cancer.Cancer biology & therapy · 2024Article
- Anti-CTLA4 treatment reduces lymphedema risk potentially through a systemic expansion of the FOXP3Nature communications · 2024Article
- Effects of Platycodon grandiflorus on doxorubicin resistance and epithelial-mesenchymal transition of breast cancer cells via the p38 mitogen-activated protein kinase pathway.Journal of molecular histology · 2024Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
It is well established that a subset of cells within primary breast cancers can undergo an epithelial-to-mesenchymal transition (EMT), although the role of EMT in metastasis remains controversial. We previously demonstrated that breast cancer cells that had undergone an oncogenic EMT could increase metastasis of neighboring cancer cells via non-canonical paracrine-mediated activation of GLI activity that is dependent on SIX1 expression in the EMT cancer cells. However, the mechanism by which these SIX1-expressing EMT cells activate GLI signaling remained unclear. In this study, we demonstrate a novel mechanism for activation of GLI-mediated signaling in epithelial breast tumor cells via EMT cell-induced production and secretion of VEGF-C. We show that VEGF-C, secreted by breast cancer cells that have undergone an EMT, promotes paracrine-mediated increases in proliferation, migration, and invasion of epithelial breast cancer cells, via non-canonical activation of GLI-signaling. We further show that the aggressive phenotypes, including metastasis, imparted by EMT cells on adjacent epithelial cancer cells can be disrupted by either inhibiting VEGF-C in EMT cells or by knocking down NRP2, a receptor which interacts with VEGF-C, in neighboring epithelial cancer cells. Interrogation of TCGA and GEO public datasets supports the relevance of this pathway in human breast cancer, demonstrating that VEGF-C strongly correlates with activation of Hedgehog signaling and EMT in the human disease. Our study suggests that the VEGF-C/NRP2/GLI axis is a novel and conserved paracrine means by which EMT cells enhance metastasis, and provides potential targets for therapeutic intervention in this heterogeneous disease.
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