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

Matsui, Chieko; Takatani‐Nakase, Tomoka; Hatano, Yuki; Kawahara, Satomi; Nakase, Ikuhiko; Takahashi, Kyoko

doi:10.1002/1873-3468.12797

Cited by 30 publications

(27 citation statements)

References 66 publications

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“…The involvement of ZIP6 in longer relapse free survival and prolonged survival of breast cancer patients with ductal carcinoma invasion has been documented [124]. Knockdown of ZIP6 in MCF-7 breast cancer cells can increase cell survival in hypoxic environments [125,126]. ZIP6 also reportedly promotes breast cancer cell invasion and metastasis, together with the high expression of E-cadherin [127,128].…”

Section: Zinc and Zinc Transporters In Other Cancersmentioning

confidence: 98%

Growth Modulatory Role of Zinc in Prostate Cancer and Application to Cancer Therapeutics

Manh

Cho

et al. 2020

IJMS

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Zinc is a group IIB heavy metal. It is an important regulator of major cell signaling pathways in most mammalian cells, functions as an antioxidant and plays a role in maintaining genomic stability. Zinc deficiency leads to severe diseases in the brain, pancreas, liver, kidneys and reproductive organs. Zinc loss occurs during tumor development in a variety of cancers. The prostate normally contains abundant intracellular zinc and zinc loss is a hallmark of the development of prostate cancer development. The underlying mechanism of this loss is not clearly understood. The knowledge that excess zinc prevents the growth of prostate cancers suggests that zinc-mediated therapeutics could be an effective approach for cancer prevention and treatment, although challenges remain. This review summarizes the specific roles of zinc in several cancer types focusing on prostate cancer. The relationship between prostate cancer and the dysregulation of zinc homeostasis is examined in detail in an effort to understand the role of zinc in prostate cancer.Int. J. Mol. Sci. 2020, 21, 2991 2 of 18 in K562 leukemia cells [11]. Withdrawal of zinc from PrEC prostate epithelial cells also stimulates breakage of single-strand DNA [12]. In addition, genes related to DNA damage response, including tumor protein p73 and MRE11, were downregulated in these cells, whereas the expression of p53 was increased. In murine fibroblasts, the addition of zinc can stimulate DNA synthesis and mitogenic signaling, whereas withdrawal of zinc reduces the secretion of growth hormone [13,14]. In Swiss 3T3 fibroblasts, ZnSO 4 can reverse the inhibitory effect of diethylenetrinitrilopentaacetate (DTPA) on thymidine incorporation into DNA, suggesting that zinc stimulates cell growth by regulating cell cycle at the G1/S phase [15]. Intracellular zinc can block the G2/M transition in human bronchial epithelial cells by upregulating p53 and p21 activity [16]. These collective findings highlight the central role of zinc in the modulation of cell proliferation, mainly by affecting DNA synthesis. Therefore, zinc homeostasis plays a key role in the development of many diseases, in which the alteration of zinc is a common event. Zinc BiologyThe human body mass contains more than 2 g of zinc. Over 90% is distributed to most tissues, with only approximately 0.1% of this metal ion circulating in plasma [17,18]. Yet, this small amount of zinc plays an important role in maintaining homeostasis in the body. Zinc is stored in most organs and tissues with approximately 60% in skeletal muscle, 30% in bone and 5% in liver and skin and the remainder distributed in other tissues that include the brain, kidneys, pancreas and heart [19] (Figure 1). Excess zinc is primarily released through gastrointestinal secretion and endogenous excretion, with minor loss through urinary excretion. Although zinc is an essential trace element used by many enzymes and transcription factors, high concentrations are toxic to the cells. Cells adapt to overcome the toxicity by maintaining the balance of ...

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Section: Zinc and Zinc Transporters In Other Cancersmentioning

confidence: 98%

Growth Modulatory Role of Zinc in Prostate Cancer and Application to Cancer Therapeutics

Manh

Cho

et al. 2020

IJMS

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“…ZIP6 was first identified in a genetic screen of estrogenresponsive factors in breast cancer tissue 15) and thus has been associated with estrogen-receptor positive breast cancer and its subsequent spread to the regional lymph nodes. 16,17) ZIP6 expression levels are downregulated in high-grade primary breast tumors. 16,17) Moreover, high ZIP6 protein expression levels correlate with a longer relapse-free survival period in patients with breast cancer, suggesting that ZIP6 levels in primary breast tumors have the potential to be a poor prognostic factor in patients with breast cancer.…”

Section: Zip6 In Estrogen-receptor Positive Breast Cancermentioning

confidence: 99%

“…16,17) ZIP6 expression levels are downregulated in high-grade primary breast tumors. 16,17) Moreover, high ZIP6 protein expression levels correlate with a longer relapse-free survival period in patients with breast cancer, suggesting that ZIP6 levels in primary breast tumors have the potential to be a poor prognostic factor in patients with breast cancer. 16) To clarify the role of e-mail: nakase@mukogawa-u.ac.jp…”

Section: Zip6 In Estrogen-receptor Positive Breast Cancermentioning

confidence: 99%

Zinc Transporters and the Progression of Breast Cancers

Takatani‐Nakase

2018

Biological & Pharmaceutical Bulletin

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Zinc (Zn) is an essential heavy metal utilized in numerous biological processes in mammals, including its recently described role as a signaling mediator. The movement of Zn in and out of cells, across membranes, is regulated by two protein families: the zinc-regulated transporter (ZRT), iron-regulated transporter (IRT)like protein (ZIP) and the Zn transporter (ZnT) families. ZIPs and ZnTs maintain intracellular Zn homeostasis and control important cellular functions through Zn signaling. Recent studies have highlighted the role of Zn transporters and Zn in disease. ZIP6, 7, and 10 contribute to human breast cancer progression. ZIP6 is associated with breast tumor grade, size, and stage, suggesting that it is a potent driving force toward malignancy; ZIP7 plays an important role in tamoxifen-resistant breast cancer cells, and ZIP10 is involved in invasion and metastasis of breast cancer cells. These Zn transporters are key molecules in the malignant process; thus, understanding Zn transporters will lead to novel diagnostic and therapeutic strategies for breast cancer. This review discusses the emerging functional roles of Zn and Zn transporters in breast cancer.

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“…The Zn 2+ ions are predominantly located within the confines of proteins and enzymes where they are essential to many biological functions [92]. The human body contains approximately 2-3 g of zinc; the amount found in the blood is kept constant (12-16 µM), however, higher concentrations (mM) are localized in many parts of the body, for example in the breast [93], prostate [94], brain [95], and pancreas [96]. The association constants range from tightly bound (log K > 11) and moderately bound (log K = 7-9) to loosely bound (log K < 7), and affect the bioavailability of Zn 2+ ions.…”

Section: Zinc Probesmentioning

confidence: 99%

Low Molecular Weight Fluorescent Probes (LMFPs) to Detect the Group 12 Metal Triad

2019

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Fluorescence sensing, of d-block elements such as Cu2+, Fe3+, Fe2+, Cd2+, Hg2+, and Zn2+ has significantly increased since the beginning of the 21st century. These particular metal ions play essential roles in biological, industrial, and environmental applications, therefore, there has been a drive to measure, detect, and remediate these metal ions. We have chosen to highlight the low molecular weight fluorescent probes (LMFPs) that undergo an optical response upon coordination with the group 12 triad (Zn2+, Cd2+, and Hg2+), as these metals have similar chemical characteristics but behave differently in the environment.

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

Cited by 30 publications

References 66 publications

Growth Modulatory Role of Zinc in Prostate Cancer and Application to Cancer Therapeutics

Growth Modulatory Role of Zinc in Prostate Cancer and Application to Cancer Therapeutics

Zinc Transporters and the Progression of Breast Cancers

Low Molecular Weight Fluorescent Probes (LMFPs) to Detect the Group 12 Metal Triad

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