Bisphenol A induces proliferative effects on both breast cancer cells and vascular endothelial cells through a shared GPER-dependent pathway in hypoxia

2017 ◽  
Vol 231 ◽  
pp. 1609-1620 ◽  
Author(s):  
Fangyi Xu ◽  
Xiaoning Wang ◽  
Nannan Wu ◽  
Shuiqing He ◽  
Weijie Yi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Bisphenol A ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Dependent Pathway

YAP Overexpression in Breast Cancer Cells Promotes Angiogenesis Through Activating Yap Signaling in Vascular Endothelial Cells

2020 ◽  
Author(s):  
Yu Yan ◽  
Qiang Song ◽  
Li Yao ◽  
Liang Zhao ◽  
Hui Cai
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Tumor Angiogenesis ◽  
Breast Cancer Cells ◽  
Vascular Endothelial Cells ◽  
Tissue Growth ◽  
Vascular Endothelial ◽  
Potential Marker

Abstract Background:The YAP signaling pathway is altered and implicated as oncogenic in human mammary cancers.However, roles of YAP signaling that regulate the breast tumor angiogenesis have remained elusive. Tumor angiogenesis is coordinated by the activation of both cancer cells and vascular endothelial cells. Whether the YAP signalingpathway can regulate the intercellular interaction between cancer cells and endothelial cellsis essentially unknown.Results: We showed here that conditioned media from YAP overexpressed breast cancer cells (CM-YAP+) could promote angiogenesis, accompanied byincreased tube formation, migration, and proliferation of human umbilical vein endothelial cells (HUVECs). Down regulation of YAP in HUVECs reversed CM-YAP+ induced angiogenesis.CM-YAP+ time-dependently activated YAP inHUVECs by dephosphorylating YAP and increasing nuclear translocation.We also identified that both G13-RhoA and PI3K/Akt signaling pathway were necessary for CM-YAP+ induced activation of YAP.Besides, connective tissue growth factor (CTGF) and angiopoietin-2 (ANG-2)actedas down-stream of YAP in HUVECs to promote angiogenesis.In addition, subcutaneous tumors nude mice model demonstrated that tumors overexpressed YAP revealed moreneovascularization in vivo.Conclusions: YAP-YAP interaction between breastcancer cells and endothelial cellscould promote tumor angiogenesis, supporting that YAP is a potential marker and target fordeveloping novel therapeutic strategies against breast cancer.

scholarly journals Effects of FSTL1 on the proliferation and motility of breast cancer cells and vascular endothelial cells

2017 ◽  
Vol 8 (6) ◽  
pp. 606-612 ◽  
Author(s):  
Yang Yang ◽  
Tianhao Mu ◽  
Te Li ◽  
Songbo Xie ◽  
Jun Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial

scholarly journals HEYL Regulates Neoangiogenesis Through Overexpression in Both Breast Tumor Epithelium and Endothelium

2021 ◽  
Vol 10 ◽  
Author(s):  
Liangfeng Han ◽  
Preethi Korangath ◽  
Nguyen K. Nguyen ◽  
Adam Diehl ◽  
Soonweng Cho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Neutralizing Antibodies ◽  
Breast Cancer Cells ◽  
Vascular Endothelial Cells ◽  
Downstream Target ◽  
Mammary Tumor Cells

Blocking tumor angiogenesis is an appealing therapeutic strategy, but to date, success has been elusive. We previously identified HEYL, a downstream target of Notch signaling, as an overexpressed gene in both breast cancer cells and as a tumor endothelial marker, suggesting that HEYL overexpression in both compartments may contribute to neoangiogenesis. Carcinomas arising in double transgenic Her2-neu/HeyL mice showed higher tumor vessel density and significantly faster growth than tumors in parental Her2/neu mice. Providing mechanistic insight, microarray-based mRNA profiling of HS578T-tet-off-HEYL human breast cancer cells revealed upregulation of several angiogenic factors including CXCL1/2/3 upon HEYL expression, which was validated by RT-qPCR and protein array analysis. Upregulation of the cytokines CXCL1/2/3 occurred through direct binding of HEYL to their promoter sequences. We found that vessel growth and migration of human vascular endothelial cells (HUVECs) was promoted by conditioned medium from HS578T-tet-off-HEYL carcinoma cells, but was blocked by neutralizing antibodies against CXCL1/2/3. Supporting these findings, suppressing HEYL expression using shRNA in MDA-MB-231 cells significantly reduced tumor growth. In addition, suppressing the action of proangiogenic cytokines induced by HEYL using a small molecule inhibitor of the CXCl1/2/3 receptor, CXCR2, in combination with the anti-VEGF monoclonal antibody, bevacizumab, significantly reduced tumor growth of MDA-MB-231 xenografts. Thus, HEYL expression in tumor epithelium has a profound effect on the vascular microenvironment in promoting neoangiogenesis. Furthermore, we show that lack of HEYL expression in endothelial cells leads to defects in neoangiogenesis, both under normal physiological conditions and in cancer. Thus, HeyL-/- mice showed impaired vessel outgrowth in the neonatal retina, while the growth of mammary tumor cells E0771 was retarded in syngeneic HeyL-/- mice compared to wild type C57/Bl6 mice. Blocking HEYL’s angiogenesis-promoting function in both tumor cells and tumor-associated endothelium may enhance efficacy of therapy targeting the tumor vasculature in breast cancer.

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