Promoting roles of the secreted frizzled-related protein 2 as a Wnt agonist in lung cancer cells

Xiao,Xiaomin; Xiao,Yingying; Wen,Ruiling; Zhang,Yuhua; Li,Xiaoxia; Wang,Haoli; Huang,Jianqiong; Liu,Jiahua; Long,Tiandi; Tang,Jun

doi:10.3892/or.2015.4221

Promoting roles of the secreted frizzled-related protein 2 as a Wnt agonist in lung cancer cells

Authors:
- Xiaomin Xiao
- Yingying Xiao
- Ruiling Wen
- Yuhua Zhang
- Xiaoxia Li
- Haoli Wang
- Jianqiong Huang
- Jiahua Liu
- Tiandi Long
- Jun Tang
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Affiliations: KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, P.R. China
Published online on: August 21, 2015 https://doi.org/10.3892/or.2015.4221
Pages: 2259-2266
Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The secreted frizzled-related protein 2 (SFRP2) plays a pivotal role in the Wnt pathway, however, it functions as an agonist or an antagonist is still controversial. We profiled SFRP2 expression in several lung cancer cell lines, and found that A549 and 95-D exhibited the lowest and the highest level of SFRP2, respectively. Then we employed the SFRP2-overexpressing plasmid and siRNA to transfect A549 and 95-D cells, respectively. Through MTT assays, we found that SFRP2 knockdown inhibited cell proliferation, and halted the 95-D cells in G1 phase of the cell cycle by downregulation of CCND1 and CDK4, indicating that SFRP2 has the ability of promoting lung cancer cell proliferation. We further checked the cell properties of migration and invasion, using wound scratch assay and Transwell assays. The data showed decreased migrated and invasive 95-D cells after SFRP2 knockdown, and the observations were the opposite in the overexpressing model, implying that SFRP2 promoted lung cancer cell invasion. Moreover, the canonical Wnt pathway was also studied through detection of β-catenin by western blotting. In the SFRP2 overexpressing model, A549 cells presented stronger expression of β-catenin compared with controls, while it was the opposite in 95-D cells. These results suggested that SFRP2 serves as a Wnt agonist in lung cancer cells. Together, the findings of this study implied that SFRP2 is not only an agonist of Wnt pathway, but also a cancer promoting protein for lung cancer, indicating SFRP2 as a promising therapeutic target for lung cancer treatment.

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