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The Emerging Role of Protein S-Nitrosylation in Cancer Metastasis

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Nitric Oxide and Cancer: Pathogenesis and Therapy

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Abstract

Nitric oxide (NO) has increasingly been recognized as an important cell signaling molecule that controls various steps of cancer development and metastasis. NO regulates a wide range of tumor-associated proteins through S-nitrosylation, a reversible coupling of a nitroso moiety to a reactive cysteine thiol (SH) group to form an S-nitrosothiol (SNO). In this article, we discuss the various roles of protein S-nitrosylation in cancer development with a focus on anoikis resistance, cell invasion and angiogenesis, which are key determinants of cancer metastasis. We specially address the effect of S-nitrosylation on protein function and discuss how this post-translational modification affects the aggressive and metastatic behaviors of cancer cells. We propose that dysregulated NO signaling is common in many, if not most, metastatic cancers and that understanding the S-nitrosylation process will facilitate the development of novel therapeutic and preventive strategies against cancers.

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Abbreviations

ABCG2:

ATP-binding cassette sub-family G member 2

c-Src:

cellular Src

DETA:

diethylenetriamine

DISC:

death-inducing signaling complex

DPTA:

dipropylenetriamine

DR:

death receptor

DTT:

dithiothreitol

ECM:

extracellular matrix

EGFR:

epidermal growth factor receptor

eNOS (NOS3):

endothelial nitric oxide synthase

ER:

estrogen receptor

ERK:

extracellular signal-regulated kinase

FAK:

focal adhesion kinase

FLIP:

FLICE-inhibitory protein

FLIP2CM:

FLIP double-cysteine mutant

JNK:

Jun N-terminal kinases

IGF:

insulin-like growth factor

iNOS (NOS2):

inducible nitric oxide synthase

MKP7:

MAP kinase phosphatase 7

MMP:

matrix metalloproteinase

NO:

nitric oxide

NOS:

nitric oxide synthase

nNOS (NOS1):

neuronal NOS

PI3K:

phosphoinositide-3-kinase

PTEN:

phosphatase and tensin homolog deleted on chromosome ten

PTM:

post-translational modification

RNOS:

reactive nitrogen-oxygen species

ROS:

reactive oxygen species

SDF-1α:

stromal cell-derived factor-1α

SH:

cysteine thiol

SNAP:

S-nitroso-N-acetylpenicillamine

SNO:

S-nitrosothiol

SNOC:

S-nitrosocysteine

VEGF:

vascular endothelial growth factor

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Acknowledgements

This work was supported by the National Institutes of Health Grants R01-HL095579 and R01-ES022968.

Conflicts of Interest

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, West Virginia University, P.O. Box 9530, 26506, Morgantown, WV, USA

    Sudjit Luanpitpong & Yon Rojanasakul Phd

  2. Mary Babb Randolph Cancer Center, West Virginia University, 26506, Morgantown, WV, USA

    Sudjit Luanpitpong & Yon Rojanasakul Phd

  3. Health Sciences Center, West Virginia University, 26506, P.O. Box 9530, Morgantown, WV, USA

    Yon Rojanasakul Phd

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  1. Sudjit Luanpitpong
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Correspondence to Yon Rojanasakul Phd .

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Editors and Affiliations

  1. Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, University of California of Los Angeles, Los Angeles, California, USA

    Benjamin Bonavida

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Luanpitpong, S., Rojanasakul, Y. (2015). The Emerging Role of Protein S-Nitrosylation in Cancer Metastasis. In: Bonavida, B. (eds) Nitric Oxide and Cancer: Pathogenesis and Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-13611-0_8

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