CCL28 promotes breast cancer growth and metastasis through MAPK-mediated cellular anti-apoptosis and pro-metastasis

Yang,Xiao Li; Liu,Kai Yi; Lin,Feng Juan; Shi,Hui Min; Ou,Zhou Luo

doi:10.3892/or.2017.5798

CCL28 promotes breast cancer growth and metastasis through MAPK-mediated cellular anti-apoptosis and pro-metastasis

Authors:
- Xiao Li Yang
- Kai Yi Liu
- Feng Juan Lin
- Hui Min Shi
- Zhou Luo Ou
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Affiliations: Breast Cancer Institute, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China, Department of Biology, College of Life and Environmental Sciences, Shanghai Normal University, Shanghai 200234, P.R. China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
Published online on: July 7, 2017 https://doi.org/10.3892/or.2017.5798
Pages: 1393-1401
Copyright: © Yang 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 one of the most commonly diagnosed cancers worldwide and the second leading cause of cancer-related deaths among females. CCL28 (mucosa-associated epithelial chemokine, MEC), a CC subfamily chemokine, has been well studied in the process of inflammation, and recently increasing evidence indicates that CCL28 is related to tumor progression. However, little is known concerning its function in breast cancer. In the present study, we generated a CCL28-overexpressing breast cancer cell line MDA-MB-231HM/CCL28 from parental MDA-MB‑231HM cells. We found that overexpression of CCL28 promoted cell proliferation and tumor formation, and also enhanced migration, invasion and metastasis both in vitro and in vivo. Mechanistic studies revealed that CCL28 mediated intracellular activation of the mitogen-activated protein kinase (MAPK) signaling pathway to promote breast cancer cell proliferation and metastasis by upregulating anti-apoptotic protein Bcl-2 and suppressing cell adhesion protein β-catenin. However, overexpression of CCL28 did not influence the expression of metastasis‑related protein matrix metalloproteinase MMP2 and MMP9 and VEGF. Tissue sample analysis from animal models also indicated that overexpression of CCL28 was associated with enhanced pERK expression and reduced β-catenin expression in breast carcinomas. Thus, our results show for the first time that CCL28 contributes to breast cancer progression through the ERK/MAPK‑mediated anti-apoptotic and metastatic signaling pathway. Antagonists of CCL28 and the MAPK signaling pathway may be used synergistically to treat breast cancer patients.

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