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IL-7 splicing variant IL-7δ5 induces EMT and metastasis of human breast cancer cell lines MCF-7 and BT-20 through activation of PI3K/Akt pathway

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Abstract

Our previous study has confirmed that IL-7δ5 (an IL-7 variant lacking exon 5) promotes breast cancer growth. However, whether IL-7δ5 is involved in tumor cell EMT and metastasis remains unclear. In this study, we investigated the preclinical effects and molecular mechanisms of IL-7δ5 on EMT and metastasis in human MCF-7 and BT-20 breast cancer cells in vitro and in vivo. The results showed that IL-7δ5 induced EMT and invasion in tumor cells, associated with up-regulation of N-cadherin and the down-regulation of E-cadherin. Furthermore, we found that IL-7δ5 induced the activation of Akt. Inhibition of PI3K/Akt pathway by LY294002 reversed the EMT transition in breast cancer cell lines MCF-7 and BT-20 induced by IL-7δ5. In addition, IL-7δ5 enhanced cancer metastasis and shortened survival time, with increased level changes of activated Akt in nude mice with breast cancer. In conclusion, our findings demonstrate that IL-7δ5 induces human breast cancer cell lines EMT and metastasis via activation of PI3K/Akt pathway. Thus, IL-7δ5 may be a potential target against human breast cancer.

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Acknowledgments

This work is supported by the National Natural Science Foundation of China (No. 81260324 and 81200308), Ministry of Education Colleges and Universities Specialized Research Fund for the Doctoral Program class of new teachers (20124503120008), Youth Foundation of Guangxi Natural Science Foundation of (No. 2012GXNSFBA053096), Youth Science Foundation of Guangxi Medical University (No. GXMUYSF14).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning, 530021, Guangxi, People’s Republic of China

    Jie Yang

  2. Department of Physiology, School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, People’s Republic of China

    Zhi Zeng

  3. Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangzhou Higher Education Mega Center, Guangdong Pharmaceutical University, 280 Wai Huan Dong Road, Guangzhou, 510006, Guangdong, People’s Republic of China

    Yuyu Peng, Jianhua Chen & Deshun Pan

  4. Nephrology Division, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, Guangxi, People’s Republic of China

    Ling Pan

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  1. Jie Yang
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Correspondence to Jie Yang.

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Jie Yang and Zhi Zeng have contributed equally to this work.

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418_2014_1222_MOESM1_ESM.tif

Supplementary Figure 1. The expression of IL-7R detected in MCF-7 and BT-20 cells. A, Immunocytochemical staining assay showing the expression and cellular location of IL-7R in MCF-7 and BT-20 cell lines. B, Western blotting data showing the expression of IL-7R in MCF-7 and BT-20 cell lines. The expression of IL-7R in HeLa cells was served as positive control. (TIFF 2390 kb)

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Yang, J., Zeng, Z., Peng, Y. et al. IL-7 splicing variant IL-7δ5 induces EMT and metastasis of human breast cancer cell lines MCF-7 and BT-20 through activation of PI3K/Akt pathway. Histochem Cell Biol 142, 401–410 (2014). https://doi.org/10.1007/s00418-014-1222-1

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