The Emerging Role of the LIV-1 Subfamily of Zinc Transporters in Breast Cancer

Taylor, KM; Morgan, Helen; Smart, Kathryn; Zahari, N. Mohamad; Pumford, Sara L; Ellis, Ian O.; Robertson, J. F. R.; Nicholson, Robert Ian

doi:10.2119/2007-00040.taylor

Cited by 208 publications

(181 citation statements)

References 54 publications

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“…The declining expression of Zip3 throughout lactation [50] in combination with a lack of phenotype noted in mice nursed from Zip3-null dams suggests Zip3 plays a minor role in mammary gland Zn uptake during lactation and illustrates that other Zip proteins likely play a role in Zn import from maternal circulation. While other Zip proteins are expressed in mammary cells [101,102] little is known regarding their contribution to Zn accumulation in the mammary gland during lactation. Taken together, it is clear that our understanding of the mechanisms that regulate Zn import from maternal circulation is incomplete.…”

Section: Mammary Gland Zinc Metabolism and Lactationmentioning

confidence: 99%

“…However, mice lacking Zip3 during pregnancy or at weaning showed impaired adaptation to Zn deficiency, suggesting that like Zip1, Zip3 plays an ancillary role during Zn deficiency and may transport several trace minerals other than Zn [24]. Zip5 expression has been detected in cultured human breast cells [102] although Zip5 function in this cell type has not been characterized. In enterocytes, Zip5 is localized to the basolateral membrane [107], where it likely imports Zn from systemic circulation.…”

Section: Introductionmentioning

confidence: 99%

“…Zip6 (LIV-1) is primarily expressed in hormonally controlled -14) import Zn into the cytoplasm, either across the plasma membrane or out of an intracellular compartment. Members of the SLC30A family (ZnT1-10) are responsible for Zn export from the cytoplasm, either across the plasma membrane into the extracellular milieu or into intracellular compartments or organelles tissues including the mammary gland, prostate and brain [14,101,102]. Zip6 was first identified as a putative marker for breast cancer although this relationship is not well understood.…”

Section: Introductionmentioning

confidence: 99%

“…Zip12 localization or function has not been delineated. Zip14 expression has also been detected in breast cancer cells [102]. Zip14 is alternatively spliced, giving rise to two isoforms Zip14A (primarily expressed in liver, duodenum, kidney, and testis) and Zip14B (primarily expressed in liver, duodenum, brain, and testis) [34].…”

Section: Introductionmentioning

confidence: 99%

“…Similar to Zip8, Zip14 transports iron [31] and cadmium as well as Zn and expression is upregulated by inflammation and LPS [59]. Similar to Zip12, Zip14 expression has been detected in MCF-7 human breast cancer cells [102] although the distinction between Zip14 isoform expression and function in the mammary gland has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

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Mammary gland zinc metabolism: regulation and dysregulation

2009

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Zinc (Zn) is required for numerous metabolic processes serving both a structural and catalytic role. The mammary gland has a unique Zn requirement resulting from the need to also transfer an extraordinary amount of Zn into milk (~0.5-1 mg Zn/day) during lactation. Impairments in this process can result in severe Zn deficiency in the nursing offspring which has adverse consequences with respect to growth and development. Moreover, dysregulated mammary gland Zn metabolism has recently been implicated in breast cancer transition, progression and metastasis, thus there is a critical need to understand the molecular mechanisms which underlie these observations. Tight regulation of Zn transporting mechanisms is critical to providing an extraordinary amount of Zn for secretion into milk as well as maintaining optimal cellular function. Expression of numerous Zn transporters has been detected in mammary gland or cultured breast cells; however, understanding the molecular mechanisms which regulate mammary Zn metabolism as well as the etiology and downstream consequences resulting from their dysregulation is largely not understood. In this review, we will summarize the current understanding of the regulation of mammary gland Zn metabolism and its regulation by reproductive hormones, with a discussion of the dysregulation of this process in breast cancer.

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Section: Mammary Gland Zinc Metabolism and Lactationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mammary gland zinc metabolism: regulation and dysregulation

2009

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Zinc and its transporter ZIP6 are key mediators of breast cancer cell survival under high glucose conditions

et al. 2017

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Recent studies have shown that hyperglycaemia is related to breast cancer progression; however, the mechanisms underlying the relationship between hyperglycaemia and breast cancer cell survival remain unknown. Here, we demonstrate that as compared to physiological glucose conditions, high glucose conditions promote a significant increase in MCF-7 cell survival under hypoxia. High glucose levels inhibit apoptosis and induce epithelial-to-mesenchymal transition, resulting in increased cell viability under hypoxic conditions. Moreover, high glucose-treated cells display significant increases in intracellular Zn levels and reduction in mRNA expression of the zinc (Zn) transporter Zrt- and Irt-like protein 6 (ZIP6) in hypoxia. ZIP6 deficiency disturbs intracellular Zn homeostasis, leading to increased cell survival in hypoxia and reduced E-cadherin expression, indicating that decreased ZIP6 expression is strongly associated with resistance to hypoxia.

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Zinc Transport: Regulation

Kambe

2004

Encyclopedia of Inorganic and Bioinorganic Chemistry

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Zinc homeostasis in cells is tightly controlled within narrow boundaries through the highly integrated processes of zinc uptake, sequestration, and efflux across the cell membrane, which enable a variety of zinc‐dependent proteins and enzymes to play physiologically important roles in numerous and varied biological responses. Thus, zinc transport proteins are essential to these processes. In general, two solute carrier (SLC) transporters, ZnT and ZIP, primarily regulate zinc transport in metazoans, but other membrane proteins (such as permeable channels) are also involved in zinc transport. Zinc exists as a divalent cation under physiological conditions, and thus it is transported across the cell membrane in this state, unlike iron and copper, which are reduced or oxidized before or after transport. This feature of zinc suggests that the expression levels of active zinc transporters at the cellular sites where they normally operate are important for defining net zinc transport, and thus the regulated expression of zinc transporters is critical for systemic and cellular zinc homeostasis. Regulation of zinc transport by ZnT and ZIP transporters is achieved by the coordination of a number of processes such as posttranslational modifications, modulation of transporter expression, and trafficking and degradation, in a zinc‐dependent or a zinc‐independent manner. In both transporters, the conserved amino acid residues in the putative intramembranous zinc‐binding sites, which are essential for zinc transport activity, appear to be involved in zinc selectivity.

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The Emerging Role of the LIV-1 Subfamily of Zinc Transporters in Breast Cancer

Cited by 208 publications

References 54 publications

Mammary gland zinc metabolism: regulation and dysregulation

Mammary gland zinc metabolism: regulation and dysregulation

Zinc and its transporter ZIP6 are key mediators of breast cancer cell survival under high glucose conditions

Zinc Transport: Regulation

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