Galectin-3 facilitates cell motility in gastric cancer by up-regulating protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1).
Galectin-3 facilitates cell motility in gastric cancer by up-regulating protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1).
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Galectin-3通过上调蛋白酶激活的受体1（PAR-1）和基质金属蛋白酶1（MMP-1），促进胃癌细胞运动。
DOI：
10.1371/journal.pone.0025103
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Chun KH
中科院分区：
文献类型：
--
作者：
Kim SJ;Shin JY;Lee KD;Bae YK;Choi IJ;Park SH;Chun KH
已知半乳糖凝集素-3调节癌症转移。然而，根本的机制尚未确定。通过基因芯片技术研究半乳糖凝集素-3基因沉默后，我们发现半乳糖凝集素-3在上调蛋白酶激活受体-1（PAR-1）和基质金属蛋白酶-1（MMP-1）PAR-1的表达，从而促进胃癌转移中起关键作用。我们检测了胃癌患者组织中半乳糖凝集素-3、PAR-1和MMP-1的表达水平，以及用特异性siRNA沉默这些蛋白质和用特异性慢病毒构建体过表达这些蛋白质的效果。我们还利用斑马鱼胚胎模型分析了胃癌细胞的体内侵袭。这些研究表明：a）半乳糖凝集素-3沉默降低PAR-1的表达。B）半乳糖凝集素-3过表达增加细胞迁移和侵袭，并且这种增加可以被PAR-1沉默逆转，表明半乳糖凝集素-3通过PAR-1上调增加细胞迁移和侵袭。c）半乳糖凝集素-3直接与AP-1转录因子相互作用，该复合物结合PAR-1启动子并驱动PAR-1转录。d）半乳糖凝集素-3还通过增加MMP-1表达来扩增PAR-1下游靶标磷酸桩蛋白。MMP-1沉默阻断半乳糖凝集素-3过表达引起的磷酸桩蛋白扩增和细胞侵袭e）半乳糖凝集素-3、PAR-1或MMP-1的沉默显著减少了斑马鱼胚胎模型中细胞向血管中的迁移。f）半乳糖凝集素-3、PAR-1和MMP-1在来自胃癌患者的恶性组织中高度表达并共定位。Galectin-3通过产生蛋白酶激活细胞表面受体，促进胃癌转移。Galectin-3有可能成为预防胃癌转移的有效药物靶点。
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. 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. 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.
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影响因子：
3
作者：
Ochieng, J;Furtak, V;Lukyanov, P
通讯作者：
Lukyanov, P
影响因子：
11.2
作者：
Adiseshaiah, Pavan;Lindner, Daniel J.;Reddy, Sekhar P.
通讯作者：
Reddy, Sekhar P.
影响因子：
14.8
作者：
Nicoli, Stefania;Presta, Marco
通讯作者：
Presta, Marco
DOI：
10.1111/j.1440-1746.2009.05810.x
发表时间：
2009-09-01
影响因子：
4.1
作者：
Kamata, Itaru;Ishikawa, Yukio;Ishii, Toshiharu
通讯作者：
Ishii, Toshiharu
影响因子：
64.5
作者：
Boire, A;Covic, L;Kuliopulos, A
通讯作者：
Kuliopulos, A