Poster No. 129 Up-Regulation of Protease-Activated Receptor-1 (PAR-1) by Galectin-3 via AP-1 Activation 5-Fluoracil mw in Human
Gastric Cancer Seok-Jun Kim 1,2 , Ji-Young Shin1, Kang-Duck Lee1, Jae-Yeol An3, Il-Ju Choi1, Kyung-Hee Chun1 1 Gastric cancer Branch, Division of translational & clinical research I, National Cancer Center Institute and Hospital, Goyang-si, Gyeonggi-do, Korea Republic, 2 Department of Biological Science, Sungkyunkwan University, Suwon-si, Gyeonggi-do, Korea Republic, 3 School of Medicine & Dental Institute, University of London, London, UK PAR-1 has been studied to play a significant role in cancer metastasis. PAR-1 is activated by thrombin and initiates the signal transduction across the membrane to activate intracellular G proteins, which regulate pathways for cell migration and adhesion. The expression of PAR-1 was also reported about the association with gastric cancer progression, however the regulation mechanism(s) of PAR-1 is still unclear. Here, we demonstrated galectin-3 regulates Bortezomib in vivo the expression of protease-activated receptor1 (PAR1), which promotes gastric cancer cell migration through
its activation. Galectin-3, a member of the β-galactoside-binding proteins, is also involved in tumor metastasis but its roles also need to study. When the expression of galectin-3 was knock-downed by small interfering RNA (siRNA), the decrease of PAR-1 expression was detected in MKN-28 gastric cancer cells. Not only PAR1 expression, galectin-3 siRNA treatment also reduced MMP-1 and PAR-1 target genes such as MMP-2 and MMP-9. Down-regulation of both of galectin-3 and PAR-1 by its siRNA resulted in decrease of cell migration and change of cell morphology to round shape. Over-expression of galectin-3 showed the increased PAR-1 expression and cell migration. However, its increasing
induced heptaminol by over-expression of galectin-3 was blocked by PAR-1 silencing, suggesting that galectin-3 promotes cell migration through PAR-1 up-regulation. To determine how galectin-3 modulates PAR-1 expression, we found out the expectation site of AP-1 binding on PAR-1 promoter and detected the interaction with galectin-3 and c-jun/fra-1. After galectin-3 silencing, c-jun and fra-1 could not bind on PAR-1 promoter by ChIP assay. Taken together, we suggest that galectin-3 increases cell motility through up-regulation of PAR-1 expression, and galectin-3 can serve as potential target molecule in the prevention and/or therapy of gastric cancer metastasis. Poster No. 130 RECK Restoration by Targeting Histone Deacetylase Blocks Hypoxia-Induced Migration and Invasion of Cancer Cells Hye Won Jeon1, Sun Hee Lee1, You Mie Lee 1 1 School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, Korea Republic Hypoxia is a strong signal for cell migration and invasion in cancer.