Activated zinc transporter ZIP7 as an indicator of anti-hormone resistance in breast cancer

ZIP7, a member of the ZIP family of zinc importers, resides on the endoplasmic reticulum membrane and transports zinc from intracellular stores to the cytoplasm after activation by CK2 phosphorylation on two serine residues (S275 and S276). ZIP7 is known to be required for the growth of anti-hormone...

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Bibliographic Details
Published in:	Metallomics Vol. 11; no. 9; pp. 1579 - 1592
Main Authors:	Ziliotto, Silvia, Gee, Julia M. W, Ellis, Ian O, Green, Andrew R, Finlay, Pauline, Gobbato, Anna, Taylor, Kathryn M
Format:	Journal Article
Language:	English
Published:	England Royal Society of Chemistry 01-09-2019
Subjects:	Antibodies Antineoplastic Agents, Hormonal - pharmacology Bioindicators Biomarkers Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - metabolism c-Fos protein Cation Transport Proteins - metabolism Chemistry Cytoplasm Drug Resistance, Neoplasm Endoplasmic reticulum ErbB-2 protein Female Hormones Humans MAP kinase MCF-7 Cells Menopause Phenotypes Phosphorylation Proto-Oncogene Mas Serine Tamoxifen Tamoxifen - pharmacology Tumors Zinc Zinc - metabolism Zinc transporter
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Summary:	ZIP7, a member of the ZIP family of zinc importers, resides on the endoplasmic reticulum membrane and transports zinc from intracellular stores to the cytoplasm after activation by CK2 phosphorylation on two serine residues (S275 and S276). ZIP7 is known to be required for the growth of anti-hormone resistant breast cancer models, especially those with acquired tamoxifen resistance developed from MCF-7. Using our new pS 275 S 276 ZIP7 antibody which only recognises activated ZIP7 (pZIP7), we have demonstrated that the hyperactivation of ZIP7 is prevalent in tamoxifen-resistant breast cancer cells. This evidence suggests that pZIP7 might have potential as a biomarker of acquired resistance to such anti-hormones in breast cancer, a current unmet clinical need. In this regard, we have also developed a new immunohistochemical assay for pZIP7 which allowed pZIP7 to be tested on a small clinical series of breast cancer tissues confirming its prevalence in such tumours and relationship to a variety of clinicopathological parameters and biomarkers previously associated with endocrine resistant phenotypes, notably increased activated MAPK signalling, expression of ErbB2, CD71 and the proto-oncogene c-Fos, as well as with increased tumour grade. Zinc transporter ZIP7 activates key downstream signalling pathways and is correlated with important clinicopathological parameters that are associated with endocrine resistance.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1756-5901 1756-591X 1756-591X
DOI:	10.1039/c9mt00136k