Review
Loss of tight junction barrier function and its role in cancer metastasis

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Abstract

As the most apical structure between epithelial and endothelial cells, tight junctions (TJ) are well known as functioning as a control for the paracellular diffusion of ions and certain molecules. It has however, become increasingly apparent that the TJ has a vital role in maintaining cell to cell integrity and that the loss of cohesion of the structure can lead to invasion and thus metastasis of cancer cells. This article will present data showing how modulation of expression of TJ molecules results in key changes in TJ barrier function leading to the successful metastasis of a number of different cancer types.

Abbreviations

BBB
blood brain barrier
BE
Barrett's esophagus
CAR
coxsackie adenovirus receptor
CIN/CIS
cervical intra-epithelial neoplasia/carcinoma in situ
CP
chronic pancreatitis
CPE
Clostridium perfringens enterotoxin
DGC
diffuse-type gastric cancer
DMSO
dimethyl sulfoxide
DCIS
ductal carcinoma in situ
EMT
epithelial-mesenchymal transition
EGFR
epidermal growth factor receptor
ELF3
E74-like factor 3
GLA
gamma linolenic acid
HGF/SF
hepatocyte growth factor/scatter factor
I
iodine
IDC
invasive ductal carcinoma
IGC
intestinal-type gastric cancer
IHC
immunohistochemistry
JAM
junctional adhesion molecule
LCIS
lobular carcinoma in situ
MAGI
membrane-associated guanylate kinase, WW and PDZ domains-containing
MAGUK
membrane-associated guanylate kinase homologs
MAPK
mitogen-activated protein kinase
MEK-2
MAPK kinase of ERK kinase MMP-2, matric metalloproteinase-2
MT
malotilate
MT1-MMP
Membrane-type 1 matrixmetallo-proteinase
MUPP-1
multi-PDZ domain protein 1
NF1
neurofibrolarosis type 1
Par
protease-activated receptors
PCP
paracellular permeability
PDZ
post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (DlgA), and zonula occludens-1 protein (zo-1)
PKC
protein kinase C
PMA
paramethoxyamphetamine
PPAC
progressive pseudorheumatoid, of childhood
PSA
prostate specific antigen
Q-PCR
quantitative polymerase chain reaction
RT-PCR
reverse-transcriptase-polymerase chain reaction
RACE
remote analysis computation for gene expression data
SCC
squamous cell cancer
SCE
specialized columnar epithelium
SqE
squamous epithelium
TCF/LEF
T-cell factor/
TER
trans-epithelial/endothelial resistance
TGF
transforming growth factor
TJ
Tight Junction/s
TNM
Tumor nodal status
VEGf
vascular endothelial growth factor

Keywords

Tight junction
Barrier function
Cancer
Metastasis

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