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The Role of Adipokines in Breast Cancer: Current Evidence and Perspectives

  • Metabolism (M Dalamaga, Section Editor)
  • Published:
Current Obesity Reports Aims and scope Submit manuscript

Abstract

Purpose

The current review shows evidence for the role of adipokines in breast cancer (BC) pathogenesis summarizing the mechanisms underlying the association between adipokines and breast malignancy. Special emphasis is given also on intriguing insights into the relationship between obesity and BC as well as on the role of novel adipokines in BC development.

Recent Findings

Recent evidence has underscored the role of the triad of obesity, insulin resistance, and adipokines in postmenopausal BC. Adipokines exert independent and joint effects on activation of major intracellular signal networks implicated in BC cell proliferation, growth, survival, invasion, and metastasis, particularly in the context of obesity, considered a systemic endocrine dysfunction characterized by chronic inflammation. To date, more than 10 adipokines have been linked to BC, and this catalog is continuously increasing. The majority of circulating adipokines, such as leptin, resistin, visfatin, apelin, lipocalin 2, osteopontin, and oncostatin M, is elevated in BC, while some adipokines such as adiponectin and irisin (adipo-myokine) are generally decreased in BC and considered protective against breast carcinogenesis.

Summary

Further evidence from basic and translational research is necessary to delineate the ontological role of adipokines and their interplay in BC pathogenesis. More large-scale clinical and longitudinal studies are awaited to assess their clinical utility in BC prognosis and follow-up. Finally, novel more effective and safer adipokine-centered therapeutic strategies could pave the way for targeted oncotherapy.

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Abbreviations

ACC:

Acetyl-coA carboxylase

ADSCs:

Adipose-derived mesenchymal stem cells

AdipoR1/R2:

adiponectin receptor 1/ 2

Akt: v-:

Akt murine thymoma viral oncogene homolog

AMPK:

5′ AMP-activated protein kinase

APPL1:

Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1

bax:

Bcl-2 associated X protein

BC:

breast cancer

bcl-xL:

B cell lymphoma-extra large

BMI:

Body mass index

CAP1:

Adenylyl cyclase–associated protein 1

CPT1B:

Carnitine palmitoyltransferase 1B

CSC:

Cancer stem cell

c-Src:

Proto-oncogene tyrosine-proteine kinase Src

DM:

Diabetes mellitus

EMT:

Epithelial-mesenchymal transition

eNampt::

Extracellular nicotinamide phosphoribosyl-transferase (eNampt)

ER:

Estrogen receptor

ERK 1/2:

Extracellular signal-regulated kinase 1/2

FAO:

Fatty acid b-oxidation

FASN:

Fatty acid synthase

GRP78:

Glucose-regulated protein 78

GTP:

Guanosine-5′-triphosphate

HER:

Human epidermal growth factor receptor

HIF-1a:

Hypoxia-inducible factor-1a

HR:

Hormone receptor

HRT:

Hormone replacement therapy

hsCRP:

High-sensitive C-reactive protein

IL:

Interleukin

IARC:

International Agency for Research on Cancer

IGF:

Insulin-like growth factor

IRS:

Insulin receptor substrate

JAK:

Janus kinase

JNK:

Jun N-terminal kinase

MAPK:

Mitogen-activated protein kinase

MMTV:

Mammary tumor virus

Lcn2:

Lipocalin 2

LEPR:

Leptin receptor

LIFR:

Leukemia inhibitory receptor

LKB1:

else known as STK11 (serine/threonine kinase 11)

MCF-7:

Michigan Cancer Foundation 7

miR:

Micro-RNA

MMP:

Matrix metalloproteinase

mTOR:

Mammalian target of rapamycin

MO25:

Scaffolding mouse 25 protein

NAD:

Nicotinamide adenine dinucleotide

Nampt:

Nicotinamide phosphoribosyl-transferase

NF-κB:

nuclear factor-κB

NGAL:

Neutrophil gelatinase–associated lipocalin

NILCO:

Notch, IL-1, and leptin

OPN:

Osteopontin

OSM:

Oncostatin M

OSMR:

OSM receptor II

OR:

Odds ratio

PBEF:

pre-B cell colony–enhancing factor

PI3K:

Phosphatidylinositol 3-kinase

PPAR:

Peroxisome proliferator–activated receptors

PR:

Progesterone receptor

RBP-4:

Retinol-binding protein

ROCK:

Rho-associated coiled coil-containing protein kinase

SHBG:

Sex hormone–binding globulin

SIRT1:

Sirtuin 1

SMD:

Standardized mean difference

STAT:

Signal transducer and activator of transcription

STRA6:

Stimulated by retinoic acid 6

STRAD:

STE20-related adaptor protein

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-α

VCAM-1:

Vascular cellular adhesion molecule-1

VEGF:

Vascular endothelial growth factor

Wnt:

Wingless-related integration site

WC:

Waist circumference

WHR:

Waist-to hip ratio

WCRF/AICR:

World Cancer Research Fund/American Institute for Cancer Research

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  1. Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527, Athens, Greece

    Gerasimos Socrates Christodoulatos, Jona Kadillari & Maria Dalamaga

  2. Laboratory of Microbiology, KAT Hospital, 2 Nikis, Kifisia, 14561, Athens, Greece

    Gerasimos Socrates Christodoulatos & Sotiria Psallida

  3. 251 Airforce General Hospital, 3 Kanellopoulou, 11525, Athens, Greece

    Nikolaos Spyrou

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Christodoulatos, G.S., Spyrou, N., Kadillari, J. et al. The Role of Adipokines in Breast Cancer: Current Evidence and Perspectives. Curr Obes Rep 8, 413–433 (2019). https://doi.org/10.1007/s13679-019-00364-y

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