Abstract
The recent report highlighted a significant association between signal transducer and activator of transcription 3 (STAT3) and Snail and LIV-1 (SLC39A6 or ZIP6), the breast cancer-associated protein that belongs to a new subfamily of zinc transporters. LIV-1 is a downstream target of STAT3, both in zebrafish and mammalian cells and provides control over epithelial-mesenchymal transition (EMT). Crucially, these observations link LIV-1, previously demonstrated to be associated with lymph node metastasis in breast cancer, to genes with a proven role in development. A putative role of LIV-1 as a regulator of E-cadherin that modulates the cell-cell adhesion is thus inferred. In present study, the correlation of LIV-1 and E-cadherin expression in human breast cancer cell MCF-7 and the effect of LIV-1 expression on the cell growth were assessed to explore the possible mechanisms associated with this observation in breast cancer. It was shown that the silencing of LIV-1 would induce the down-expression of E-cadherin. There was opposite results if the cells were overexpressed with LIV-1. In addition, the results showed that promotion effect after silencing of LIV-1 and inhibition effect after overexpression of LIV-1 in transfected cells. To our knowledge, this is the first evidence that the expression of E-cadherin could be regulated by the zinc transporter LIV-1. The results suggest that there is an association of LIV-1 expression with less aggressive tumors due to high E-cadherin expression because of high LIV-1 expression. LIV-1 may be a regulator of E-cadherin.
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Abbreviations
- STAT3:
-
Signal transducer and activator of transcription 3
- EMT:
-
Epithelial-mesenchymal transition
- ZIP:
-
Zrt-, Irt-like proteins
- LZT:
-
LIV-1 subfamily of ZIP zinc transporters
- RT-PCR:
-
Reverse transcription polymerase chain reaction
- MTT:
-
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide
- MT:
-
Metallothioneins
- CDF:
-
Cation diffusion facilitator
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Acknowledgments
We thank Dr. K. M. Taylor (Tenovus Cancer Research Centre, Welsh School of Pharmacy, Cardiff University, U.K.) for kindly providing us the LIV-1 recombinant. We also thank Dr. Qiuli Chen for her excellent technical assistance.
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H. Shen and H. Qin are contributed equally to this work.
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Shen, H., Qin, H. & Guo, J. Concordant correlation of LIV-1 and E-cadherin expression in human breast cancer cell MCF-7. Mol Biol Rep 36, 653–659 (2009). https://doi.org/10.1007/s11033-008-9225-4
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DOI: https://doi.org/10.1007/s11033-008-9225-4