ssig-h3 regulates store-operated Ca2+ entry and promotes the invasion of human hepatocellular carcinoma cells
ssig-h3 regulates store-operated Ca2+ entry and promotes the invasion of human hepatocellular carcinoma cells
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ssig-h3 调节钙池操纵的 Ca2+ 进入并促进人肝细胞癌细胞的侵袭
DOI：
10.1042/cbi20100916
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发表时间：
2011-08-01
影响因子：
3.9
通讯作者：
Jiang, Jian-Li
中科院分区：
文献类型：
--
作者：
Guo, Yun-Shan;Tang, Juan;Jiang, Jian-Li
sign -h3是一种tgf - β（转化生长因子β）诱导的细胞外基质（ECM）蛋白，可诱导基质金属蛋白酶（MMPs）的分泌。然而，诱导机制尚未建立。本研究将靶向ssig-h3的sirna（小干扰rna）转染到SMMC-7721细胞[HCC（人肝细胞癌）细胞系]中，以抑制ssig-h3的表达。我们发现NiCl2，一种有效的细胞外Ca2+进入阻断剂，减少了ssign -h3诱导的MMP-2和-9的分泌。进一步的研究表明，ssig-h3水平的降低降低了MMP-2和-9的分泌，而细胞外Ca2+浓度的增加则增强了MMP-2和-9的分泌。NO（一氧化氮）供体SNAP （S-nitroso-N-acetylpenicillamine）和8-Br-cGMP（8-溴- cgmp）抑制thapsigargin诱导的人SMMC-7721细胞侵袭电位中的Ca2+进入和MMP分泌。下调sigg -h3可显著增强8-Br-cGMP和SNAP的抑制作用。sign -h3减弱NO/ cgmp敏感的存储操作Ca2+进入的负调控。我们的研究结果表明，sign -h3的表达可能在调节储存操作的Ca2+进入中发挥重要作用，从而增加HOC细胞的侵袭电位。
ssig-h3 is a TGF-beta (transforming growth factor beta)-induced ECM (extracellular matrix) protein that induces the secretion of MMPs (matrix metalloproteinases). However, the mechanism of induction is yet to be established. In this study, siRNAs (small interfering RNAs) targeted against ssig-h3 were transfected into SMMC-7721 cells [a HCC (human hepatocellular carcinoma) cell line] to knockdown the expression of ssig-h3. We found that NiCl2, a potent blocker of extracellular Ca2+ entry, reduced ssig-h3-induced secretion of MMP-2 and -9. Further investigation suggested that reduction in the levels of ssig-h3 decreased the secretion of MMP-2 and -9 that was enhanced by an increase in the concentration of extracellular Ca2+. SNAP (S-nitroso-N-acetylpenicillamine), a NO (nitric oxide) donor, and 8-Br-cGMP (8-bromo-cGMP) inhibited thapsigargin-induced Ca2+ entry and MMP secretion in the invasive potential of human SMMC-7721 cells. Further, the inhibitory effects of 8-Br-cGMP and SNAP could be significantly enhanced by down-regulating ssig-h3. ssig-h3 attenuates the negative regulation of NO/cGMP-sensitive store-operated Ca2+ entry. Our findings suggest that the expression of ssig-h3 might play an important role in the regulation of store-operated Ca2+ entry to increase the invasive potential of HOC cells.