JWA suppresses the invasion of human breast carcinoma cells 
by downregulating the expression of CXCR4

Xu,Lingyun; Cheng,Lin; Yang,Fangliang; Pei,Bei; Liu,Xiaoan; Zhou,Jianwei; Zhu,Yulan; Wang,Shui

doi:10.3892/mmr.2018.8866

JWA suppresses the invasion of human breast carcinoma cells by downregulating the expression of CXCR4

Authors:
- Lingyun Xu
- Lin Cheng
- Fangliang Yang
- Bei Pei
- Xiaoan Liu
- Jianwei Zhou
- Yulan Zhu
- Shui Wang
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Affiliations: Department of Breast Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213003, P.R. China, Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: April 11, 2018 https://doi.org/10.3892/mmr.2018.8866
Pages: 8137-8144
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer is the second leading cause of cancer‑associated mortality, and metastatic breast cancer is responsible for 90% of patient mortalities. Given that JWA represses the proliferation, invasion and metastasis of a number of other human tumor cells, including melanoma, esophageal, hepatocellular and gastric carcinomas, via mitogen‑activated protein kinase or integrin signaling, the present study investigated the expression and function of JWA in human breast cancers. The results showed that the expression level of JWA was significantly reduced in human primary breast cancers when compared with the paired adjacent tissues. Downregulating JWA enhanced, while overexpressing JWA suppressed, the migration and invasion abilities of the two breast cancer cell lines, MDA‑MB‑468 and MDA‑MB‑231, without affecting their proliferations in vitro. In addition, JWA negatively regulated the surface expression of CXCR4 in the two cell lines via proteasome degradation, though not via transcriptional inhibition. Functionally, normalizing the disturbed expressions of CXCR4 largely reversed the inhibitory effect of JWA on cell invasion. These data demonstrated that JWA suppressed the migration/invasion of breast carcinoma cells by downregulating the expression of CXCR4, and suggested that JWA may harbor prognostic and therapeutic potential in patients with breast cancer.

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