Abstract
WNT1 inducible signaling pathway protein 1 (WISP1) plays a key role in many cellular functions in a highly tissue-specific manner; however the role of WISP1 in breast cancer is still poorly understood. Here, we demonstrate that WISP1 acts as an oncogene in human breast cancer. We demonstrated that human breast cancer tissues had higher WISP1 mRNA expression than normal breast tissues and that treatment of recombinant WISP1 enhanced breast cancer cell proliferation. Further, ectopic expression of WISP1 increased the growth of breast cancer cells in vitro and in vivo. WISP1 transfection also induced epithelial-mesenchymal-transition (EMT) in MCF-7 cells, leading to higher migration and invasion. During this EMT-inducing process, E-cadherin was repressed and N-cadherin, snail, and β-catenin were upregulated. Filamentous actin (F-actin) remodeling and polarization were also observed after WISP1 transfection into MCF-7 cells. Moreover, forced overexpression of WISP1 blocked the expression of NDRG1, a breast cancer tumor suppressor gene. Our study provides novel evidence that WISP1-modulated NDRG1 gene expression is dependent on a DNA fragment (−128 to +46) located within the human NDRG1 promoter. Thus, we concluded that WISP1 is a human breast cancer oncogene and is a potential therapeutic target.
Highlights
WNT1 inducible signaling pathway protein 1 (WISP1) plays a key role in many cellular functions in a highly tissue-specific manner; the role of WISP1 in breast cancer is still poorly understood
We demonstrated that human breast cancer tissues had higher WISP1 mRNA expression than normal breast tissues and that treatment of recombinant WISP1 enhanced breast cancer cell proliferation
RT-qPCR results showed that the mean between 20 pairs of normal and cancerous tissues is DDCt 5 22.87 1 0.53, indicating that WISP1 mRNA expression is higher in breast cancer tissues as compared to normal breast tissues (Fig. 1A)
Summary
WNT1 inducible signaling pathway protein 1 (WISP1) plays a key role in many cellular functions in a highly tissue-specific manner; the role of WISP1 in breast cancer is still poorly understood. We demonstrate that WISP1 acts as an oncogene in human breast cancer. Ectopic expression of WISP1 increased the growth of breast cancer cells in vitro and in vivo. WISP1 transfection induced epithelial-mesenchymal-transition (EMT) in MCF-7 cells, leading to higher migration and invasion. During this EMT-inducing process, E-cadherin was repressed and N-cadherin, snail, and b-catenin were upregulated. Forced overexpression of WISP1 blocked the expression of NDRG1, a breast cancer tumor suppressor gene. We concluded that WISP1 is a human breast cancer oncogene and is a potential therapeutic target. Overexpression of WISP1 down-regulated the invasion and migration of lung cancer cells, leading to reduced www.nature.com/scientificreports metastatic potential[11]. NDRG1 represses breast cancer cell proliferation and invasion when ectopically overexpressed[19]
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