Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.3 (
collagenase
)
18,340
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Lipolysis-stimulated lipoprotein receptor
(
LSR
) is a novel molecule present at tricellular contacts which recruits tricellulin (TRIC), a molecular component of tricellular tight junctions (tTJs).
LSR
and TRIC are colocalized with the bicellular tight junction (bTJ) protein claudin (CLDN)-1-based tight junction strands at tricellular corners. Knockdown of
LSR
in normal epithelial cells affects tTJ formation and the epithelial barrier function. In cancer cells knockdown of
LSR
has been demonstrated to increase cell invasion. However, the detailed mechanisms of how the downregulation of
LSR
enhances cell invasion in cancer remain unclear. In the present study, knockdown of
LSR
by small interfering RNA (siRNA) in Sawano human endometrial adenocarcinoma cells induced cell invasion. In
LSR
-knockdown Sawano cells, upregulation of CLDN-1 protein, which contributes to the cell invasion via matrix metalloproteinases (MMPs), was observed compared with the control group by western blotting and immunostaining. Knockdown of
LSR
significantly induced Sp1 transcription factor activity in the CLDN-1 promoter region. In
LSR
-knockdown Sawano cells, DNA microarray analysis demonstrated that
MMP-1
, MMP-2 and MMP-10 mRNA levels were increased, and the protein levels of membrane-type 1-MMP, MMP-2, MMP-9 and MMP-10 were shown to be increased on western blots. Knockdown of CLDN-1 with siRNA prevented the upregulation of cell invasion induced by the knockdown of
LSR
in Sawano cells. On the invasive front of human endometrial carcinoma tissue samples, a decrease in
LSR
and increase in CLDN-1 protein levels were observed using immunohistochemical methods. In conclusion, the results indicate that the downregulation of
LSR
promotes cell invasion of human endometrial cancer via CLDN-1 mediation of MMPs. This mechanism is important for studying the association of tTJs with the cellular invasion of cancer.
...
PMID:Downregulation of lipolysis-stimulated lipoprotein receptor promotes cell invasion via claudin-1-mediated matrix metalloproteinases in human endometrial cancer. 2915 17
