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Obesity, Energy Balance, and Cancer: A Mechanistic Perspective

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Advances in Nutrition and Cancer

Part of the book series: Cancer Treatment and Research ((CTAR,volume 159))

Abstract

Nearly 36 % of adults and 20 % of children in the USA are obese, defined as a body mass index (BMI) ≥30 kg/m2. Obesity, which is accompanied by metabolic dysregulation often manifesting in the metabolic syndrome, is an established risk factor for many cancers. Within the growth-promoting, proinflammatory environment of the obese state, cross talk between macrophages, adipocytes, and epithelial cells occurs via obesity-associated hormones, cytokines, and other mediators that may enhance cancer risk and/or progression. This chapter synthesizes the evidence on key biological mechanisms underlying the obesity–cancer link, with particular emphasis on obesity-associated enhancements in growth factor signaling, inflammation, and vascular integrity processes, as well as obesity-dependent microenvironmental perturbations, including the epithelial-to-mesenchymal transition. These interrelated pathways represent possible mechanistic targets for disrupting the obesity–cancer link.

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Abbreviations

AMPK:

AMP-activated kinase

BMI:

Body mass index

CR:

Caloric restriction

COX-2:

Cyclooxygenase-2

DIO:

Diet-induced obesity

EMT:

Epithelial-to-mesenchymal transition

FGF-2:

Fibroblast growth factor-2

IGF-1:

Insulin-like growth factor-1

JAK:

Janus kinase

mTOR:

Mammalian target of rapamycin

MCP-1:

Monocyte chemoattractant protein-1

NF-kB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

PAI-1:

Plasminogen activator inhibitor-1

PI3K:

Phosphatidylinositol 3-kinase

STAT:

Signal transducer activator of transcription

TNF-α:

Tumor necrosis factor-alpha

tPA:

Tissue-type plasminogen activators

uPA:

Urokinase-type plasminogen activators

VEGF:

Vascular endothelial growth factor

ZEB1:

Zinc finger E-box-binding homeobox 1

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Acknowledgments

Dr. S. Hursting is funded, in part, by grants from the National Cancer Institute (R01CA129409 and R01CA135306), the Breast Cancer Research Foundation (UTA09-001068), and the National Institute of Environmental Health Sciences (P30ES007784).

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Authors and Affiliations

  1. Department of Nutritional Sciences, Dell Pediatric Research Institute, University of Texas at Austin, 1400 Barbara Jordan Blvd, Austin, TX, 78723, United States

    Stephen D. Hursting

  2. Department of Molecular Carcinogenesis, University of Texas-MD Anderson Cancer Center, Smithville, TX, United States

    Stephen D. Hursting

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  1. Stephen D. Hursting
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Correspondence to Stephen D. Hursting .

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Editors and Affiliations

  1. Dept. of Biochemistry and Biophysics, Second University of Naples, Naples, Italy

    Vincenzo Zappia

  2. Clinical and Experimental Medicine, University of Naples "Federico II", Naples, Italy

    Salvatore Panico

  3. Institute of Food Sciences National Research Council, Avellino, Italy

    Gian Luigi Russo

  4. Dept. of Experimental Oncology, National Cancer Institute, Naples, Italy

    Alfredo Budillon

  5. Dept. of Biochemistry and Biophysics, Second University of Naples, Naples, Italy

    Fulvio Della Ragione

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Hursting, S.D. (2014). Obesity, Energy Balance, and Cancer: A Mechanistic Perspective. In: Zappia, V., Panico, S., Russo, G., Budillon, A., Della Ragione, F. (eds) Advances in Nutrition and Cancer. Cancer Treatment and Research, vol 159. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38007-5_2

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  • DOI: https://doi.org/10.1007/978-3-642-38007-5_2

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