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Published on: August 3, 2017
Snail promotes the generation of vascular endothelium by breast cancer cells
Zhenyu Chang1,2, Yanan Zhang1,3, Jie Liu1
1Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Collaborative Innovation Center for Cancer Medicine, 100850, Beijing, China.
Abstract:
A further understanding of tumor angiogenesis is urgently needed due to the limited therapeutic efficacy of anti-angiogenesis agents. However, the origin of endothelial cells (EC) in tumors remains widely elusive and controversial. Snail has been thoroughly elucidated as a master regulator of the epithelial-mesenchymal transition (EMT), but its role in endothelium generation is not yet established. In this study, we reported a new and unexpected function of Snail in endothelium generation by breast cancer cells. We showed that high Snail-expressing breast cancer cells isolated from patients showed more endothelium generated from these cells. Expression of Snail was positively correlated with endothelial markers in breast cancer patients. The ectopic expression of Snail induced endothelial marker expression, tube formation and DiI-AcLDL uptake of breast cancer cells in vitro, and enhanced tumor growth and microvessel density in vivo. Snail-mediated endothelium generation depended on VEGF and Sox2. Mechanistically, Snail promoted the expression of VEGF and Sox2 through recruiting the p300 activator complex to these promoters. We showed the dual function of Snail in tumor initiation and angiogenesis in vivo and in vitro through activation of Sox2 and VEGF, suggesting Snail may be an ideal target for cancer therapy.
Insights
Snail, a key regulator in cancer, unexpectedly drives breast cancer cell endothelium generation. This discovery highlights Snail
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Limited efficacy of anti-angiogenesis agents necessitates understanding tumor angiogenesis.
- The origin of tumor endothelial cells (EC) is poorly understood.
- Snail's role in endothelium generation is not established.
Purpose of the Study:
- Investigate the novel function of Snail in endothelium generation by breast cancer cells.
- Determine the correlation between Snail expression and endothelial markers in patients.
- Elucidate the mechanism of Snail-mediated endothelium generation.
Main Methods:
- Analysis of Snail-expressing breast cancer cells from patients.
- In vitro assays for endothelial marker expression, tube formation, and DiI-AcLDL uptake.
- In vivo studies of tumor growth and microvessel density.
- Investigation of Snail's interaction with VEGF and Sox2.
Main Results:
- High Snail expression in breast cancer cells correlated with increased endothelium generation.
- Snail expression positively correlated with endothelial markers in patients.
- Ectopic Snail expression induced endothelial characteristics and enhanced tumor growth and angiogenesis in vivo.
- Snail-mediated endothelium generation required VEGF and Sox2, with Snail recruiting p300 to their promoters.
Conclusions:
- Snail plays a dual role in breast cancer initiation and angiogenesis.
- Snail promotes endothelium generation by breast cancer cells via VEGF and Sox2 activation.
- Snail represents a potential therapeutic target for cancer therapy.
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