YAP Overexpression in Breast Cancer Cells Promotes Angiogenesis through Activating YAP Signaling in Vascular
Yu Yan1, Qiang Song2, Li Yao3
1Department of Breast Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Analytical Cellular Pathology (Amsterdam)
|October 13, 2022
Summary
YAP signaling promotes breast tumor angiogenesis by enhancing communication between cancer and endothelial cells. Targeting YAP may offer new breast cancer treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The YAP signaling pathway is implicated in human breast cancers.
- The specific role of YAP in regulating breast tumor angiogenesis remains unclear.
- Tumor angiogenesis involves coordinated activation of cancer and vascular endothelial cells.
Purpose of the Study:
- To investigate the role of YAP in breast tumor angiogenesis.
- To determine if YAP signaling regulates intercellular communication between cancer and endothelial cells.
- To explore YAP's impact on vascular endothelial cell behavior.
Main Methods:
- In vitro assays evaluated YAP's effects on endothelial cell migration, proliferation, and tube formation.
- Western blotting, immunofluorescence, and immunohistochemistry assessed protein expression in YAP, G13-RhoA, and PI3K/Akt pathways.
- In vivo studies utilized a breast cancer xenograft mouse model to assess tumor angiogenesis.
Main Results:
- Conditioned media from YAP-overexpressing breast cancer cells promoted angiogenesis in endothelial cells.
- YAP activation in endothelial cells was dependent on G13-RhoA and PI3K/Akt pathways.
- Connective tissue growth factor (CTGF) and angiopoietin-2 (ANG-2) were identified as downstream mediators of YAP-induced angiogenesis.
- Tumors overexpressing YAP showed increased neovascularization in vivo.
Conclusions:
- YAP-mediated interactions between cancer cells and endothelial cells promote tumor angiogenesis.
- YAP is a potential biomarker and therapeutic target for breast cancer treatment.
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