Tunicamycin-induced ER stress regulates chemokine CCL5 expression and secretion via STAT3 followed by decreased transmigration of MCF-7 breast cancer cells

Zhang,Yimin; Liao,Shichong; Fan,Wei; Wei,Wen; Wang,Changhua; Sun,Shengrong

doi:10.3892/or.2014.3479

Tunicamycin-induced ER stress regulates chemokine CCL5 expression and secretion via STAT3 followed by decreased transmigration of MCF-7 breast cancer cells

Authors:
- Yimin Zhang
- Shichong Liao
- Wei Fan
- Wen Wei
- Changhua Wang
- Shengrong Sun
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Affiliations: Department of Breast and Thyroid Surgery, Renmin Hospital, Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: September 16, 2014 https://doi.org/10.3892/or.2014.3479
Pages: 2769-2776

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Abstract

Chemokine C-C motif ligand 5 (CCL5) is an important marker related to the progression of breast cancer and is upregulated in cancer cells. However, the mechanism of the overexpression of CCL5 in tumours has not yet been clarified. The present study aimed to investigate the role of endoplasmic reticulum (ER) stress in regulating CCL5 expression and its relationship with signal transducer and activator of transcription 3 (STAT3). Meanwhile, the effect of tunicamycin, a classical ER stress inducer, and CCL5 on the transmigration of human breast cancer MCF-7 cells was observed and analysed. Compared with the normal breast epithelial tissues, expression levels of CCL5, STAT3 and CHOP, an indicator of ER stress, were significantly upregulated in breast cancer tissues. In human breast cancer MCF-7 cells, ER stress activator tunicamycin increased the expression of CCL5, STAT3 and CHOP in a time- and concentration-dependent manner. Moreover, tunicamycin-induced CCL5 expression was positively related to upregulation of unphosphorylated STAT3 (U-STAT3) but negatively related to STAT3 phosphorylation at the Tyr705 site. Furthermore, ER stress inhibited CCL5 secretion and transmigration of MCF-7 cells. This study also showed that extracellular rhCCL5 induced transmigration of MCF-7 cells which was partially blocked by the CCR5 monoclonal antibody, while knockdown of endogenous expression of CCL5 did not affect the transmigration of the cells. In conclusion, ER stress induced endogenous expression of CCL5 via elevating U-STAT3 expression; however, ER stress inhibited CCL5 secretion, which in turn, decreased the transmigration of breast cancer MCF-7 cells.

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