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 2019-09, Vol.11 (9), p.1579-1592
Main Authors: Ziliotto, Silvia, Gee, Julia M. W, Ellis, Ian O, Green, Andrew R, Finlay, Pauline, Gobbato, Anna, Taylor, Kathryn M
Format: Article
Language:English
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.
ISSN:1756-5901
1756-591X
1756-591X
DOI:10.1039/c9mt00136k