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

Qianying Tao; Yingxue Qi; Jiayi Gu; Die Yu; Yuxin Lu; Jianwen Liu; Xin Liang

doi:10.1016/j.taap.2022.115927

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

Toxicol Appl Pharmacol. 2022 Apr 1:440:115927. doi: 10.1016/j.taap.2022.115927. Epub 2022 Feb 19.

Authors

Qianying Tao¹, Yingxue Qi¹, Jiayi Gu¹, Die Yu², Yuxin Lu¹, Jianwen Liu¹, Xin Liang³

Affiliations

¹ Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
² Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China; Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
³ Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China. Electronic address: xin.liang@ecust.edu.cn.

PMID: 35192807
DOI: 10.1016/j.taap.2022.115927

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.

Keywords: Angiogenesis; Breast cancer; Metastasis; PI3K/Akt; vWF.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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