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Visfatin, Obesity, and Cancer

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Adipocytokines, Energy Balance, and Cancer

Part of the book series: Energy Balance and Cancer ((EBAC,volume 12))

Abstract

Cancer represents an important public health concern. Overweight, obesity, and metabolic syndrome influence the risk and prognosis of several disease states including cancer. Metabolic changes related to visceral obesity could contribute to a dysfunctional adipose tissue provoking chronic subclinical inflammation, insulin resistance, and abnormal production of adipokines. Visfatin, found in the visceral adipose tissue, known also as nicotinamide phosphoribosyltransferase (Nampt) and pre-B-cell colony-enhancing factor (PBEF), acts as a multifaceted molecule with a triple action: a cytokine, a growth factor, and an enzyme. It exerts a pivotal role in a multitude of metabolic and stress responses and cellular bioenergetics, specifically nicotinamide adenine dinucleotide (NAD) synthesis. Visfatin/Nampt exhibits antiapoptotic, proliferative, pro-inflammatory, pro-angiogenic, and metastatic properties. The insulin-mimetic function of visfatin/Nampt remains a controversial issue. Circulating visfatin/Nampt is enhanced in many cancers, including obesity-associated malignancies. It is associated with bad prognosis and higher tumor stage and grade. Plasma visfatin/Nampt may be a novel risk factor as well as a surrogate clinical marker in cancer therapeutics. Moreover, pharmacologic neutralization of visfatin/Nampt employing agents that reduce its levels or downregulate signaling pathways downstream of visfatin/Nampt could be promising anticancer treatments. In this book chapter, we will particularly focus on both intracellular and extracellular visfatin/Nampt’s contribution to cancer pathophysiology as well as on the mechanisms underlying the connection between visfatin/Nampt and cancer. Further research is required in order to conclude whether visfatin/Nampt may be a therapeutic target in the pharmacological arsenal for cancer.

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Abbreviations

ADP:

Mono-adenosine diphosphate

ALL:

Acute lymphoblastic leukemia

AML:

Acute myeloid leukemia

AMPK:

5′ AMP-activated protein kinase

ATP:

Adenosine triphosphate

BC:

Breast cancer

BMI:

Body mass index

Cdks:

Cyclin-dependent kinases

C.I.:

Confidence interval

CLL:

Chronic lymphocytic leukemia

CML:

Chronic myeloid leukemia

CRP:

C-reactive protein

CtBPs:

Mammalian COOH-terminal binding proteins

ER:

Estrogen receptor

ERKs:

Extracellular signal-regulated kinases

HL:

Hodgkin lymphoma

ICAM-1 :

Intercellular adhesion molecule-1

IL:

Interleukin

IGF:

Insulin-like growth factor

IRS:

Insulin receptor substrate

MAPK:

Mitogen-activated protein kinase

MDS:

Myelodysplastic syndrome

MM:

Multiple myeloma

MPD:

Myeloproliferative disorders

MMPs:

Matrix metalloproteinases

NAD:

Nicotinamide adenine dinucleotide

Nampt:

Nicotinamide phosphoribosyltransferase

NHL:

Non-Hodgkin lymphoma

NF-kB:

Nuclear factor-kB

OR:

Odds ratio

PARP:

Poly (ADP-ribose) polymerase

PBEF:

Pre-B-cell colony-enhancing factor

PI3K :

Phosphatidylinositol 3-kinase

PTEN:

Phosphatase and tensin homolog

SirT:

Silent mating type information regulation, sirtuin

SNPs:

Single-nucleotide polymorphisms

STAT:

Signal transducer and activator of transcription

TNF-α :

Tumor necrosis factor-α

Tiam1:

T-cell lymphoma invasion and metastasis-inducing protein 1

VCAM-1 :

Vascular cell adhesion molecule-1

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Department of Clinical Biochemistry, University of Athens, “Attikon” General University Hospital, 1 Rimini Street, Chaidari, 12462, Athens, Greece

    Maria Dalamaga M.D., M.Sc., M.P.H., Ph.D. & Gerasimos Socrates Christodoulatos M.D.

  2. Department of Biological Chemistry-Clinical Biochemistry, University of Athens Medical School, 75 Mikras Asias Street, Goudi, 11527, Athens, Greece

    Maria Dalamaga M.D., M.Sc., M.P.H., Ph.D.

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  1. Maria Dalamaga M.D., M.Sc., M.P.H., Ph.D.
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  1. Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA

    Ofer Reizes

  2. Center for Science, Health and Society, Case Western Reserve University, Cleveland, Ohio, USA

    Nathan A. Berger

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Dalamaga, M., Christodoulatos, G.S. (2017). Visfatin, Obesity, and Cancer. In: Reizes, O., Berger, N. (eds) Adipocytokines, Energy Balance, and Cancer. Energy Balance and Cancer, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-41677-9_6

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