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Adipokines and epithelial-mesenchymal transition (EMT) in cancer

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Abstract

Obesity is a significant risk factor for cancer development. Within the tumor microenvironment, adipocytes interact with cancer cells, immune cells, fibroblasts and endothelial cells, and orchestrate several signaling pathways by secreting bioactive molecules, including adipokines. Adipokines or adipocytokines are produced predominantly by adipocytes and function as autocrine, paracrine and endocrine mediators. Adipokines can exert pro- and anti-inflammatory functions, and they play a pivotal role in the state of chronic low-grade inflammation that characterizes obesity. Epithelial-mesenchymal transition (EMT), a complex biological process whereby epithelial cells acquire the invasive, migratory mesenchymal phenotype is well-known to be implicated in cancer progression and metastasis. Emerging evidence suggests that there is a link between adipokines and EMT. This may contribute to the correlation that has been documented between obesity and cancer progression. This review summarizes the existing body of evidence supporting an association between the process of EMT in cancer and the adipokines leptin, adiponectin, resistin, visfatin/NAMPT, lipocalin-2/NGAL, as well as other newly discovered adipokines including chemerin, nesfatin-1/nucleobindin-2, AZGP1, SFRP5 and FABP4.

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Abbreviations

ADSF:

Adipocyte-specific secretory factor

BMI:

Body mass index

CAP1:

Adenylyl cyclase-associated protein-1

CCAs:

Cancer-associated adipocytes

CCL2:

C–C motif chemokine 2

COX-2:

Cyclooxygenase-2

EMT:

Epithelial-mesenchymal transition

eNAMPT:

Extracellular nicotinamide phosphoribosyltransferase

FABP4:

Fatty acid binding protein-4

FAK:

Focal adhesion kinase

FIZZ3:

Protein found in inflammatory zone 3

HCC:

Hepatocellular carcinoma

iNAMPT:

Intracellular Nicotinamide phosphoribosyltransferase

LCN2:

Lipocalin-2

MCP-1:

Monocyte chemotactic protein 1

MET:

Mesenchymal-epithelial transition

MMPs:

Matrix metalloproteinases

NAMPT:

Nicotinamide phosphoribosyltransferase

NGAL:

Neutrophil gelatinase-associated lipocalin

PAI-1:

Plasminogen activator inhibitor-1

SFRP5:

Secreted frizzled-related protein 5

TADCs:

Tumor-associated dendritic cells

TLR4:

Toll-like receptor 4

TNBC:

Triple negative breast cancer

TNF:

Tumor necrosis factor

ZAG:

Zinc-alpha2-glycoprotein

ZO-1:

Zonula occludens-1

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  1. Department of General Surgery, University General Hospital of Patras, Rion, Greece

    Ioanna Akrida

  2. Department of Anatomy-Histology-Embryology, University of Patras Medical School, Rion, Greece

    Ioanna Akrida & Helen Papadaki

  3. Department of Surgery, Department of Anatomy-Histology-Embryology, School of Medicine, University of Patras, 26504, Rion, Greece

    Ioanna Akrida

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Conceptualization: HP and IA. IA reviewed the literature, prepared the manuscript and created the figures. HP made the final editing and revision of the manuscript and offered her expert opinion.

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Akrida, I., Papadaki, H. Adipokines and epithelial-mesenchymal transition (EMT) in cancer. Mol Cell Biochem 478, 2419–2433 (2023). https://doi.org/10.1007/s11010-023-04670-x

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