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Metastasis review: from bench to bedside

  • Review
  • Published:
Tumor Biology

Abstract

Cancer is the final result of uninhibited cell growth that involves an enormous group of associated diseases. One major aspect of cancer is when cells attack adjacent components of the body and spread to other organs, named metastasis, which is the major cause of cancer-related mortality. In developing this process, metastatic cells must successfully negotiate a series of complex steps, including dissociation, invasion, intravasation, extravasation, and dormancy regulated by various signaling pathways. In this review, we will focus on the recent studies and collect a comprehensive encyclopedia in molecular basis of metastasis, and then we will discuss some new potential therapeutics which target the metastasis pathways. Understanding the new aspects on molecular mechanisms and signaling pathways controlling tumor cell metastasis is critical for the development of therapeutic strategies for cancer patients that would be valuable for researchers in both fields of molecular and clinical oncology.

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Abbreviations

GFs:

Growth factors

MMPs:

Matrix metalloproteinases

CTCs:

Circulating tumor cells

ECM:

Extracellular matrix

ROS:

Reactive oxygen species

FAs:

Focal adhesions

FAK:

Focal adhesion kinase

MAPK:

Mitogen-activated protein kinase

uPAR:

Uroplasminogen activator receptor

PIP3:

Phosphatidylinositol 3

PI3K:

Phosphatidylinositol 3 kinase

Src:

Pronounced “sarc” as it is short for “sarcoma”

ILK:

Integrin-linked kinase

PKB (known as Akt):

Protein kinase B

GSK3β:

Glycogen synthase kinase 3 beta

EGF:

Epidermal growth factor

TNF-α:

Tumor necrosis factor alpha

IL:

Interleukin

IgSF:

Immunoglobulin superfamily

CAMs:

Cell adhesion molecules

MCAM:

Melanoma CAM

L1CAM:

L1 protein family CAM

NCAM:

Neural CAM

PECAM:

Platelet endothelial CAM

ALCAM:

Aplysia CAM

ICAM-1:

Intercellular CAM-1

VCAM-1:

Vascular cell CAM-1

HA:

Hyaluronan

VEGFR-2:

Vascular endothelial growth factor-2

MT-MMPs:

Membrane-type MMPs

TIMPs:

Tissue inhibitors of metalloproteases

bFGF:

Basic fibroblast growth factor

Pro-TGFα:

Protransforming growth factor alpha

PAR:

Protease-activated receptor

Fas-L:

Fas-ligand

FADD:

Fas-associated protein with death domain

TSP:

Thrombospondin

LRP:

Lipoprotein receptor-related protein

ERKs:

Extracellular signal-regulated kinases

CXCL5:

Chemokine C-X-C motif ligand-5

MCP-3:

Monocyte chemoattractant protein-3

SDF-1:

Stromal cell-derived factor-1

ADAM-10:

A disintegrin and metalloproteinase domain-containing protein 10

IGFs:

Insulin-like growth factors

IGFBP:

IGF binding protein

CECs:

Capillary endothelial cells

NF-κB:

Nuclear factor-κb

cis-ACCP:

cis-2-Aminocyclohexylcarbamoyl phosphonic acid

SPs:

Serine proteases

PAI-1:

Plasminogen activator inhibitor-1

Serpin:

Serine proteinase inhibitors

HGF:

Hepatocyte growth factor

STAT3:

Signal transducer and activator of transcription 3

Cath-D:

Cathepsin D

MHC:

Major histocompatibility complex

CAFs:

Cancer-associated fibroblasts

TAMs:

Tumor-associated macrophages

PLC:

Phosphoinositide-specific phospholipase C

CAT:

Collective to amoeboid transition

EMT:

Epithelial to mesenchymal transition

MAT:

Mesenchymal to amoeboid transition

CSF1:

Colony-stimulating factor-1

TrkB:

Also known as TrkB tyrosine kinase or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase receptor type 2

Ras:

An abbreviation of “rat sarcoma”

TF:

Tissue factor

EphA5:

Eph receptor A5

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Acknowledgments

This study was supported by Tehran University of Medical Sciences.

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The authors report no conflicts of interest. The authors alone are responsible for the content of the paper.

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  1. Cancer Research Center, Tehran University of Medical Sciences, Tehran, 1419733141, Iran

    Ali Mohammad Alizadeh, Sadaf Shiri & Sadaf Farsinejad

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  1. Ali Mohammad Alizadeh
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Correspondence to Ali Mohammad Alizadeh.

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Alizadeh, A.M., Shiri, S. & Farsinejad, S. Metastasis review: from bench to bedside. Tumor Biol. 35, 8483–8523 (2014). https://doi.org/10.1007/s13277-014-2421-z

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