title: Galectin-3 facilitates cell motility in gastric cancer by up-regulating protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1).
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Gastric Cancer Branch, Division of Translational and Clinical Research I, National Cancer Center Research Institute and Hospital, Jungbalsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, Republic of Korea.
authors.forename: Seok-Jun
authors.initials: SJ
authors.lastname: Kim
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Shin
authors.forename: Kang-Duck
authors.initials: KD
authors.lastname: Lee
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Bae
authors.forename: Il-Ju
authors.initials: IJ
authors.lastname: Choi
authors.forename: Seok Hee
authors.initials: SH
authors.lastname: Park
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Chun
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D016086:Lentivirus / Q000235:genetics; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D037502:Galectin 3; D044463:Receptor, PAR-1; D020781:Matrix Metalloproteinase 1