Osterix promotes the migration and angiogenesis of breast cancer by upregulation of S100A4 expression

Shuang Qu; Jiahui Wu; Qianyi Bao; Bing Yao; Rui Duan; Xiang Chen; Lingyun Li; Hongyan Yuan; Yucui Jin; Changyan Ma

doi:10.1111/jcmm.14012

Osterix promotes the migration and angiogenesis of breast cancer by upregulation of S100A4 expression

J Cell Mol Med. 2019 Feb;23(2):1116-1127. doi: 10.1111/jcmm.14012. Epub 2018 Nov 18.

Authors

Shuang Qu^{1

2}, Jiahui Wu^{1

2}, Qianyi Bao^{1

2}, Bing Yao^{1

2}, Rui Duan^{1

2}, Xiang Chen³, Lingyun Li^{1

2}, Hongyan Yuan⁴, Yucui Jin^{1

2}, Changyan Ma^{1

2}

Affiliations

¹ Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
² Department of Medical Genetics, Nanjing Medical University, Nanjing, China.
³ Department of General Surgery, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China.
⁴ Department of Oncology and Lombardi Comprehensive Cancer Center, Lombardi Comprehensive Cancer Center, Washington, District of Columbia.

Abstract

As a key transcription factor required for bone formation, osterix (OSX) has been reported to be overexpressed in various cancers, however, its roles in breast cancer progression remain poorly understood. In this study, we demonstrated that OSX was highly expressed in metastatic breast cancer cells. Moreover, it could upregulate the expression of S100 calcium binding protein A4 (S100A4) and potentiate breast cancer cell migration and tumor angiogenesis in vitro and in vivo. Importantly, inhibition of S100A4 impaired OSX-induced cell migration and capillary-like tube formation. Restored S100A4 expression rescued OSX-short hairpin RNA-suppressed cell migration and capillary-like tube formation. Moreover, the expression levels of OSX and S100A4 correlated significantly in human breast tumors. Our study suggested that OSX acts as an oncogenic driver in cell migration and tumor angiogenesis, and may serve as a potential therapeutic target for human breast cancer treatment.

Keywords: S100A4; angiogenesis; breast cancer; migration; osterix.

Publication types

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

MeSH terms

Breast Neoplasms / genetics*
Breast Neoplasms / pathology
Cell Line
Cell Line, Tumor
Cell Movement / genetics*
Female
Gene Expression Regulation, Neoplastic / genetics
Human Umbilical Vein Endothelial Cells
Humans
MCF-7 Cells
Neovascularization, Pathologic / genetics*
Neovascularization, Pathologic / pathology
RNA, Small Interfering / genetics
S100 Calcium-Binding Protein A4 / genetics*
Sp7 Transcription Factor / genetics*
Transcriptional Activation / genetics
Up-Regulation / genetics*

Substances

RNA, Small Interfering
S100 Calcium-Binding Protein A4
Sp7 Transcription Factor
SP7 protein, human
S100A4 protein, human