期刊
FEBS LETTERS
卷 591, 期 20, 页码 3348-3359出版社
WILEY
DOI: 10.1002/1873-3468.12797
关键词
breast cancer cells MCF-7; hyperglycaemia; hypoxia; zinc; zinc transporter
资金
- Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan
- Japan Society for the Promotion of Science [15K07955]
- Grants-in-Aid for Scientific Research [16H02612, 15K07955] Funding Source: KAKEN
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 Zn2+ levels and reduction in mRNA expression of the zinc (Zn) transporter Zrt- and Irt-like protein 6 (ZIP6) in hypoxia. ZIP6 deficiency disturbs intracellular Zn2+ 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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