AMF/PGI transactivates the MMP-3 gene through the activation of Src-RhoA-phosphatidylinositol 3-kinase signaling to induce hepatoma cell migration

Wen-Ling Shih; Ming-Huei Liao; Feng-Ling Yu; Ping-Yuan Lin; Hsue-Yin Hsu; Shu-Jun Chiu

doi:10.1016/j.canlet.2008.05.005

AMF/PGI transactivates the MMP-3 gene through the activation of Src-RhoA-phosphatidylinositol 3-kinase signaling to induce hepatoma cell migration

Cancer Lett. 2008 Nov 8;270(2):202-17. doi: 10.1016/j.canlet.2008.05.005. Epub 2008 Jun 20.

Authors

Wen-Ling Shih¹, Ming-Huei Liao, Feng-Ling Yu, Ping-Yuan Lin, Hsue-Yin Hsu, Shu-Jun Chiu

Affiliation

¹ Graduate Institute, Department of Life Science, Tzu-Chi University, 701 Section 3, Chung-Yang Road, Hualien 970, Taiwan. shihwl@mail.tcu.edu.tw

PMID: 18571835
DOI: 10.1016/j.canlet.2008.05.005

Abstract

We have previously shown that AMF/PGI induces hepatoma cell migration through the induction of MMP-3. This work investigates how AMF/PGI activates the MMP-3 gene. We demonstrated that AMF/PGI transactivates the MMP-3 gene promoter through AP-1. The transactivation and induction of cell migration effect of AMF/PGI directly correlates with its enzymatic activity. Various analyses showed that AMF/PGI stimulated the Src-RhoA-PI3-kinase signaling pathway, and these three signaling molecules could form a complex. Our results demonstrate a new mechanism of AMF/PGI-induced cell migration and a link between Src-RhoA-PI3-kinase, AP-1, MMP-3 and hepatoma cell migration.

Publication types

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

MeSH terms

Carcinoma, Hepatocellular / enzymology*
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
Cell Movement* / drug effects
Cell Movement* / genetics
Cloning, Molecular
Enzyme Inhibitors / pharmacology
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Glucose-6-Phosphate Isomerase / genetics
Glucose-6-Phosphate Isomerase / metabolism*
Humans
Liver Neoplasms / enzymology*
Liver Neoplasms / genetics
Liver Neoplasms / pathology
Matrix Metalloproteinase 3 / genetics
Matrix Metalloproteinase 3 / metabolism*
Phosphatidylinositol 3-Kinases / metabolism*
Phosphoinositide-3 Kinase Inhibitors
Point Mutation
Promoter Regions, Genetic
Signal Transduction* / drug effects
Signal Transduction* / genetics
Transcription Factor AP-1 / metabolism
Transcriptional Activation
Transfection
rhoA GTP-Binding Protein / antagonists & inhibitors
rhoA GTP-Binding Protein / metabolism*
src-Family Kinases / antagonists & inhibitors
src-Family Kinases / metabolism*

Substances

Enzyme Inhibitors
Phosphoinositide-3 Kinase Inhibitors
Transcription Factor AP-1
RHOA protein, human
src-Family Kinases
MMP3 protein, human
Matrix Metalloproteinase 3
rhoA GTP-Binding Protein
Glucose-6-Phosphate Isomerase