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The emerging role of zinc transporters in cellular homeostasis and cancer
Open accessAbstract
Zinc is an essential micronutrient that plays a role in the structural or enzymatic functions of many cellular proteins. Cellular zinc homeostasis involves the opposing action of two families of metal transporters: the ZnT (SLC30) family that functions to reduce cytoplasmic zinc concentrations and the ZIP (SLC39) family that functions to increase cytoplasmic zinc concentrations. Fluctuations in intracellular zinc levels mediated by these transporter families affect signaling pathways involved in normal cell development, growth, differentiation and death. Consequently, changes in zinc transporter localization and function resulting in zinc dyshomeostasis have pathophysiological effects. Zinc dyshomeostasis has been implicated in the progression of cancer. Here we review recent progress toward understanding the structural basis for zinc transport by ZnT and ZIP family proteins, as well as highlight the roles of zinc as a signaling molecule in physiological conditions and in various cancers. As zinc is emerging as an important signaling molecule in the development and progression of cancer, the ZnT and ZIP transporters that regulate cellular zinc homeostasis are promising candidates for targeted cancer therapy.
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Cites
Counting the Zinc-Proteins Encoded in the Human Genome
Andreini, C., Banci, L., Bertini, I., & Rosato, A. (2006) · Journal of Proteome Research · doi:10.1021/pr050361j · Cited by 1,109
Zinc biochemistry: From a single zinc enzyme to a key element of life
Maret, W. (2013) · Advances in Nutrition · doi:10.3945/an.112.003038 · Cited by 818
Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism, and geophagia
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Zinc transporter ZIP8 (SLC39A8) and zinc influence IFN-γ expression in activated human T cells
Aydemir, T. B., Liuzzi, J. P., McClellan, S., & Cousins, R. J. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.1208759 · Cited by 229
Neurulation and neurite extension require the zinc transporter ZIP12 ( slc39a12 )
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Cited by
Zinc-based biomaterials for regeneration and therapy
Su, Y., Cockerill, I., Wang, Y., Qin, Y.-X., Chang, L., Zheng, Y., & Zhu, D. (2019) · Trends in biotechnology · doi:10.1016/j.tibtech.2018.10.009 · Cited by 417
Chen, B., Yu, P., Chan, W. N., Xie, F., Zhang, Y., Liang, L., Leung, K. T., Lo, K. W., Yu, J., Tse, G. M. K., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01679-y · Cited by 420
Role of zinc in health and disease
Stiles, L. I., Ferrao, K., & Mehta, K. J. (2024) · Clinical and Experimental Medicine · doi:10.1007/s10238-024-01302-6 · Cited by 275
The special stemness functions of Tbx3 in stem cells and cancer development
Dong, L., Lyu, X., Faleti, O. D., & He, M.-L. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.09.010 · Cited by 41
Metadata
- Authors
- Bafaro, E., Liu, Y., Xu, Y., & Dempski, R. E.
- Venue
- Signal Transduction and Targeted Therapy
- Published
- 2017-07-28
- Volume
- 2
- Issue
- 1
- ISSN
- 2059-3635 (ISSN-L)
- OpenAlex
- W2741568582
- Cited by
- 307
- References
- 6
- FWCI
- 14.93
- Type
- journal article
- Language
- en
- Open access
- gold
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