Galectin-3 Facilitates Cell Motility in Gastric Cancer by Up-Regulating Protease-Activated Receptor-1(PAR-1) and Matrix Metalloproteinase-1(MMP-1)
- Authors
- Kim, S.J., Shin, J.Y., Lee, K.D., Bae, Y.K., Choi, I.J., Park, S.H., and Chun, K.H.
- ID
- ZDB-PUB-111021-1
- Date
- 2011
- Source
- PLoS One 6(9): e25103 (Journal)
- Registered Authors
- Bae, Young Ki
- Keywords
- none
- MeSH Terms
-
- Animals
- Blotting, Western
- Cell Line, Tumor
- Cell Movement/genetics
- Cell Movement/physiology*
- Chromatin Immunoprecipitation
- Galectin 3/genetics
- Galectin 3/metabolism*
- Genetic Vectors/genetics
- Humans
- Immunohistochemistry
- Immunoprecipitation
- In Vitro Techniques
- Lentivirus/genetics
- Matrix Metalloproteinase 1/genetics
- Matrix Metalloproteinase 1/metabolism*
- Oligonucleotide Array Sequence Analysis
- Receptor, PAR-1/genetics
- Receptor, PAR-1/metabolism*
- Reverse Transcriptase Polymerase Chain Reaction
- Stomach Neoplasms/genetics
- Stomach Neoplasms/metabolism*
- Zebrafish
- PubMed
- 21966428 Full text @ PLoS One
Background
Galectin-3 is known to regulate cancer metastasis. However, the underlying mechanism has not been defined. Through the DNA microarray studies after galectin-3 silencing, we demonstrated here that galectin-3 plays a key role in up-regulating the expressions of protease-activated receptor-1(PAR-1) and matrix metalloproteinase-1(MMP-1) PAR-1 thereby promoting gastric cancer metastasis.
Methodology/Principal Findings
We examined the expression levels of Galectin-3, PAR-1, and MMP-1 in gastric cancer patient tissues and also the effects of silencing these proteins with specific siRNAs and of over-expressing them using specific lenti-viral constructs. We also employed zebrafish embryo model for analysis of in vivo gastric cancer cell invasion. These studies demonstrated that: a) galectin-3 silencing decreases the expression of PAR-1. b) galectin-3 over-expression increases cell migration and invasion and this increase can be reversed by PAR-1 silencing, indicating that galectin-3 increases cell migration and invasion via PAR-1 up-regulation. c) galectin-3 directly interacts with AP-1 transcriptional factor, and this complex binds to PAR-1 promoter and drives PAR-1 transcription. d) galectin-3 also amplifies phospho-paxillin, a PAR-1 downstream target, by increasing MMP-1 expression. MMP-1 silencing blocks phospho-paxillin amplification and cell invasion caused by galectin-3 over-expression. e) Silencing of either galectin-3, PAR-1 or MMP-1 significantly reduced cell migration into the vessels in zebrafish embryo model. f) Galectin-3, PAR-1, and MMP-1 are highly expressed and co-localized in malignant tissues from gastric cancer patients.
Conclusions/Significance
Galectin-3 plays the key role of activating cell surface receptor through production of protease and boosts gastric cancer metastasis. Galectin-3 has the potential to serve as a useful pharmacological target for prevention of gastric cancer metastasis.