Int J Biol Sci 2019; 15(10):2139-2155. doi:10.7150/ijbs.35541

Research Paper

EFEMP2 suppresses epithelial-mesenchymal transition via Wnt/β-catenin signaling pathway in human bladder cancer

Qiang Zhou1,#, Song Chen1,#, Mengxin Lu1, Yongwen Luo1, Gang Wang2,3,4, Yu Xiao1,2,3,4, Lingao Ju2,3,✉, Xinghuan Wang1,5,6,✉

1. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
2. Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China
3. Human Genetics Resource Preservation Center of Hubei Province, Wuhan, China
4. Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
5. Medical Research Institute, Wuhan University, Wuhan, China
6. Urological Clinical Research Center of Laparoscopy in Hubei Province, Wuhan, China
# These authors contributed equally to this work.

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Citation:
Zhou Q, Chen S, Lu M, Luo Y, Wang G, Xiao Y, Ju L, Wang X. EFEMP2 suppresses epithelial-mesenchymal transition via Wnt/β-catenin signaling pathway in human bladder cancer. Int J Biol Sci 2019; 15(10):2139-2155. doi:10.7150/ijbs.35541. Available from http://www.ijbs.com/v15p2139.htm

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Abstract

Epidermal growth factor-containing fibulin-like extracellular matrix protein 2 (EFEMP2), an extracellular matrix protein, is highly associated with tumor invasion and metastasis. However, influenced by the tumor microenvironment, EFEMP2 played different roles in different tumors. The current study focused on exploring the role of EFEMP2 in bladder cancer (BCa). The results suggested that the expression of EFEMP2 was significantly higher in normal tissues and cells compared with BCa samples and cells. And we found a negative correlation between EFEMP2 expression and high tumor stage, high tumor grade, patients with low EFEMP2 expression had a much poorer survival than those patients with high EFEMP2 expression. The multivariate analysis revealed that low EFEMP2 expression was a high-risk predictor of BCa survival. Furthermore, cell proliferation, migration and metastasis can be obviously affected by the changes of EFEMP2 expression both in vitro and in vivo.

Our results also turned out that knockdown of EFEMP2 could significantly reduce the epithelial marker (E-cadherin), increase mesenchymal markers (N-cadherin, Vimentin, Snail and Slug) as well as the key factors of Wnt/β-catenin signaling pathway (β-catenin, c-Myc and cyclin D1). The reversed results were found in the EFEMP2 overexpression cells. Importantly, the related expression changes of epithelial-mesenchymal transition (EMT) markers and Wnt/β-catenin signaling pathway factors induced by EFEMP2 upregulation or downregulation can be rescued using LiCl or XAV939. Collectively, our observations revealed that EFEMP2 is a blocker of tumor progression and metastasis in BCa.

Keywords: EFEMP2, bladder cancer, epithelial-mesenchymal transition, Wnt/β-catenin signaling pathway