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Zinc and Zinc-Dependent Proteins in Cancer and Chemotherapeutics

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Essential and Non-essential Metals

Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

Abstract

Zinc (Zn) is an essential element critical for numerous protein structures and catalytic functions. This chapter focuses on the importance of homeostatic concentrations and appropriate subcellular distributions of Zn within cells, as well as the structural and catalytic roles Zn plays for many important enzymes. The mechanisms and factors by which homeostatic levels of intracellular Zn are maintained are discussed, as well as means by which Zn is distributed within the cell. In addition, several important proteins that require Zn for catalytic activity, such as matrix metalloproteinases and lysine deacetylases, and structural functions, such as the transcription factor p53, are reviewed. Associations between the dysregulation of Zn-dependent proteins or intracellular Zn homeostasis and the development and progression of several cancers are detailed, with emphasis placed on mechanistic links related to Zn. Finally, the various chemotherapeutic strategies that have been developed to either modify intracellular Zn levels or directly target cancer-associated proteins that involve Zn and potential future chemotherapeutic targets are evaluated.

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Abbreviations

ECM:

Extracellular matrix

ER:

Estrogen receptor

FGF-2:

Fibroblast growth factor 2

GLI:

Glioma-associated oncogene

HAT:

Histone acetyltransferase

HCC:

Hepatocellular carcinoma

HDAC:

Histone deacetylase

Hh:

Hedgehog

IL-2:

Interleukin-2

KDAC:

Lysine deacetylase

MMP:

Matrix metalloproteinase

MT:

Metallothionein

mtp53:

Mutant p53

PML:

Promyelocytic leukemia gene

RAR-α:

Retinoic acid receptor α

ROS:

Reactive oxygen species

RRE:

Ras-responsive element

RREB1:

Ras-responsive element-binding protein 1

Snai1:

Snail homolog 1

Sp1:

Specificity protein 1

TGF-β:

Transforming growth factor β

TIMP:

Tissue inhibitor of metalloproteinase

ZIP:

Zrt-, Irt-related proteins

Zn:

Zinc

ZnT:

Zinc transporters

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Authors and Affiliations

  1. Oak Ridge Institute for Science and Education (ORISE) Fellow at the National Health and Environmental Effects Research Laboratory, U.S. EPA, Research Triangle Park, NC, USA

    Jenna Guynn

  2. Oak Ridge Institute for Science and Education (ORISE) Fellow at the National Center for Environmental Assessment, U.S. Environmental Protection Agency (EPA), Research Triangle Park, NC, USA

    Elizabeth A. W. Chan

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  1. Jenna Guynn
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Correspondence to Jenna Guynn .

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  1. Natl Ctr Envtl Assessment Office of Res and Devt, Research Triangle Park, North Carolina, USA

    Anuradha Mudipalli

  2. Professor of Environmental Medicine, New York University, Tuxedo, New York, USA

    Judith T. Zelikoff

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Guynn, J., Chan, E.A.W. (2017). Zinc and Zinc-Dependent Proteins in Cancer and Chemotherapeutics. In: Mudipalli, A., Zelikoff, J. (eds) Essential and Non-essential Metals. Molecular and Integrative Toxicology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-55448-8_4

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