Breast cancer cells-derived Von Willebrand Factor promotes VEGF-A-related angiogenesis through PI3K/Akt-miR-205-5p signaling pathway.

Abstract

The metastasis and angiogenesis of breast cancer has always been a difficult problem for treatment. It has recently been discovered that Von Willebrand Factor (vWF), in addition to hemostasis, also plays a role in tumor metastasis and angiogenesis. We noticed that besides endothelial cells, breast cancer cells (MDA-MB-231 and MCF-7) could also express vWF. In vitro experiments showed that knocking down vWF inhibited breast cancer cell metastasis. And we found that overexpression of vWF significantly promoted VEGF-A-dependent vascular proliferation in vitro by activating the PI3K/Akt signaling pathway. Further studies indicated that inhibition of PI3K/Akt signaling pathway up-regulated the expression of miR-205-5p, and miR-205-5p could bind to the 3'UTR region of VEGF-A to hinder the production of VEGF-A. Furthermore, when a spontaneous lung metastasis model was established in Balb/c female mice, knockdown of vWF in 4 T1 cells resulted in a decrease in tumor blood vessel density and effectively inhibited lung metastasis, accompanied by a decrease in the expression level of VEGF-A and an increase in the expression level of miR-205-5p. In summary, our findings provide experimental evidence that overexpression of vWF in breast cancer cells down-regulates the expression of miR-205-5p and up-regulates the expression of VEGF-A through the PI3K/Akt signaling pathway, thereby promoting tumor angiogenesis and metastasis.

• Authors: Qianying Tao, Yingxue Qi, Jiayi Gu, Die Yu, Yuxin Lu, Jianwen Liu, Xin Liang
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 440 Pg. 115927 (04 01 2022) ISSN: 1096-0333 [Electronic] United States
• PMID: 35192807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• MIRN205 microRNA, human
• MicroRNAs
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• von Willebrand Factor
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Breast Neoplasms (pathology)
• Cell Proliferation
• Endothelial Cells (metabolism)
• Female
• Humans
• Lung Neoplasms (metabolism)
• Mice
• MicroRNAs (metabolism)
• Neovascularization, Pathologic (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (physiology)
• Vascular Endothelial Growth Factor A (metabolism)
• von Willebrand Factor (metabolism)