ECRG2 regulates ECM degradation and uPAR/FPRL1 pathway contributing cell invasion/migration

Xiaolong Cheng; Shih-Hsin Lu; Yongping Cui

doi:10.1016/j.canlet.2009.09.001

ECRG2 regulates ECM degradation and uPAR/FPRL1 pathway contributing cell invasion/migration

Cancer Lett. 2010 Apr 1;290(1):87-95. doi: 10.1016/j.canlet.2009.09.001. Epub 2009 Sep 30.

Authors

Xiaolong Cheng¹, Shih-Hsin Lu, Yongping Cui

Affiliation

¹ Department of Anatomy, Shanxi Medical University, Taiyuan, PR China.

PMID: 19796867
DOI: 10.1016/j.canlet.2009.09.001

Abstract

ECRG2 is a novel tumor suppressor gene that shows sequence similarity to KAZAL-type serine protease inhibitor. We have previously demonstrated ECRG2 inhibits migration/invasion of lung cancer PG cells. However, the mechanism by which ECRG2 performs these activities remains unknown. In this study, we found that ECRG2 inhibits proteolysis activity of uPA/plasmin and MMP2, and substantially reduces the ability of HT1080 and HCT-116 cells to invade ECM. Moreover, we demonstrated ECRG2 prevents the cleavage of uPAR, disrupts the association of sD2D3 with FPRL1, and that disruption impairs FPRL1 function. Conversely, depletion of ECRG2 not only markedly increased proteolysis activity of uPA/plasmin and MMP2 but also enhanced the association of uPAR with FPRL1, stimulated cell migration/invasion. Together, our results provide evidence that ECRG2 regulates invasion/migration partly through ECM degradation and uPA/uPAR/FPRL1 pathway, and may represent a novel therapeutic target for cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Movement
Extracellular Matrix
Fluorescent Antibody Technique
Gene Expression
Gene Expression Regulation, Neoplastic
HCT116 Cells
Humans
Immunoblotting
Immunoprecipitation
Matrix Metalloproteinase 2 / metabolism
Neoplasm Invasiveness / genetics*
Proteinase Inhibitory Proteins, Secretory
Receptors, Formyl Peptide / genetics
Receptors, Formyl Peptide / metabolism*
Receptors, Lipoxin / genetics
Receptors, Lipoxin / metabolism*
Receptors, Urokinase Plasminogen Activator / genetics
Receptors, Urokinase Plasminogen Activator / metabolism*
Serine Peptidase Inhibitors, Kazal Type
Signal Transduction / physiology*
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / metabolism*

Substances

FPR2 protein, human
Proteinase Inhibitory Proteins, Secretory
Receptors, Formyl Peptide
Receptors, Lipoxin
Receptors, Urokinase Plasminogen Activator
SPINK7 protein, human
Serine Peptidase Inhibitors, Kazal Type
Tumor Suppressor Proteins
Matrix Metalloproteinase 2