Osterix transcriptional factor is involved in the metastasis of human breast cancers

Abstract

Abstract. The transcriptional factor Osterix is specifically expressed in bone tissues to regulate the differentiation and maturation of osteoblasts. Recent studies have also identified the expression of Osterix in a number of cancer tissues, such as kidney and lung cancers. However, the association of Osterix with the metastasis of breast cancers has never been reported. The present study, for the first time, provides evidence supporting the involvement of Osterix in breast cancer metastasis. Western blotting was employed to investigate the expression of Osterix in a number of human breast cancer cell lines with different metastatic features. Gain-of-function and loss-of-function experiments were performed in MCF7 cells (low level of metastasis) and MDA-MB-361 cells (high level of metastasis). The expression of several metastasis-associated genes was analyzed by western blotting and quantitative polymerase chain reaction. A firefly luciferase-based reporter gene assay was conducted in order to study whether Osterix regulated the promoter activities of the MMP2 and MMP9 genes, which play critical roles in cancer metastasis. The results showed that Osterix was highly expressed in the MDA-MB-231 and MDA-MB-361 cells, but was not detectable in the MCF7 cells. The overexpression of Osterix in the MCF7 cells promoted the expression of VEGF, MMP9 and β-catenin, while downregulating the expression of E-cadherin. In addition, suppression of Osterix expression in the MDA-MB-361 cells reversed the alteration of VEGF, MMP9, β-catenin and E-cadherin expression. A reporter gene assay suggested that Osterix activated MMP2 and MMP9 promoter activity. In conclusion, Osterix is involved in the metastasis of human breast cancer and may be a target for the efficient treatment of human breast cancers.

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

“…Osterix (OSX), also known as SP7, is a zinc finger transcription factor that is usually expressed in osteoblasts to regulate osteoblast differentiation and maturation . The expression of OSX had been suggested to be limited to bone tissues; however, recent studies identified that OSX was overexpressed in various cancer tissues, such as osteosarcoma, prostate cancer and breast cancer . Nevertheless, there have been few studies on the role of OSX in carcinogenesis.…”

“…4 The expression of OSX had been suggested to be limited to bone tissues; however, recent studies identified that OSX was overexpressed in various cancer tissues, such as osteosarcoma, prostate cancer and breast cancer. [5][6][7] Nevertheless, there have been few studies on the role of OSX in carcinogenesis. OSX expression in osteoblasts is regulated by various factors, including bone morphogenetic protein 2 (BMP2), Msh homeobox 2 (MSX2), myogenic differentiation (MYOD), and distal-less homeobox 5 (DLX5).…”

“…[8][9][10] However, its downstream signaling remains largely elusive. Although a recent study indicated that OSX could alter the expression profile of several metastasis-associated genes, such as those encoding vascular endothelial growth factor (VEGF), matric metalloproteinase 9 (MMP-9), β-catenin, and E-cadherin in human breast cancer cells, 7 whether the expression of OSX is critical for cancer metastasis is unknown, and the underlying mechanism remains to be defined. S100 calcium binding protein A4 (S100A4) is involved in a variety of physiological functions, such as cell motility, adhesion, proliferation, and metastasis.…”

Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14

“…Osx-null mice with the complete absence of intramembranous and endochondral bone formation died immediately after birth [14]. Recently, Dai et al reported that Osx is involved in the metastasis of human breast cancers [15]. However, the precise roles of Osx in breast cancer remain unclear and need to be elucidated.…”

Runt‐Related Transcription Factor 2 (Runx2) Is Responsible for Galectin‐3 Overexpression in Human Thyroid Carcinoma

“…The promoter region of many MMP genes also contain binding site for ETS family of oncoproteins. Additionally, it has been recently shown that osterix (Transcription factor Sp7) could regulate the expression of MMP-2 and 9 by interacting their promoter region in human breast cancer cells [Dai et al, 2015]. [Folgueras et al, 2004].…”