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Breast Cancer
Published in: Breast Cancer 5/2019

Open Access 01-09-2019 | Breast Cancer | Original Article

PIM1 is responsible for IL-6-induced breast cancer cell EMT and stemness via c-myc activation

Authors: Xueqiang Gao, Xiangping Liu, Yangyong Lu, Yu Wang, Weihong Cao, Xiaoyi Liu, Haiyan Hu, Haibo Wang

Published in: Breast Cancer | Issue 5/2019

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Abstract

Background

Interleukin-6 (IL-6) has been demonstrated to be a critical factor for breast cancer malignancy. However, the molecular mechanisms by which IL-6 induce breast cancer cells epithelial–mesenchymal-transition (EMT) and stemness remain elusive.

Methods

Breast cancer cell lines T47D and MCF7 were exposed to IL-6, the expression of PIM1 was examined by quantitative real-time PCR (qRT-PCR) and western blot. Luciferase reporter assay was used to determine the transcriptional modulation of PIM1 by IL-6 and STAT3 inhibitor. Transwell assay was used to detect the invading ability of breast cancer cells induced by IL-6 or PIM1. The expressions of EMT and stemness markers were determined by qRT-PCR.

Results

IL-6 promoted PIM1 expression in a dose- and time-dependent manner, and this induction could be abrogated by inhibiting STAT3 activation, subsequently suppressing the transcriptional level of PIM1. Moreover, we noticed that knocking down of PIM1 in cells which was exposed to IL-6 significantly impaired the invasion ability and the expression of EMT and stemness markers. On the contrary, overexpression of PIM1 promoted cell invasion and upregulated the expression of EMT and stemness markers. In addition, we demonstrated that c-myc, the cofactor of PIM1, involved in the pro-oncogenic roles of PIM1. Knocking down of c-myc attenuated the PIM1-induced cell EMT and stemness.

Conclusion

This study proposed the upregulation of PIM1 by IL-6 contributed to breast cancer cell aggressiveness and targeting PIM1 or c-myc could be novel approaches for breast cancer treatment.
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Metadata
Title
PIM1 is responsible for IL-6-induced breast cancer cell EMT and stemness via c-myc activation
Authors
Xueqiang Gao
Xiangping Liu
Yangyong Lu
Yu Wang
Weihong Cao
Xiaoyi Liu
Haiyan Hu
Haibo Wang
Publication date
01-09-2019
Publisher
Springer Japan
Published in
Breast Cancer / Issue 5/2019
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-019-00966-3

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