Gli1 contributes to the invasiveness of pancreatic cancer through matrix metalloproteinase-9 activation
Gli1 contributes to the invasiveness of pancreatic cancer through matrix metalloproteinase-9 activation
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DOI：
10.1111/j.1349-7006.2008.00822.x
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发表时间：
2008-07-01
期刊：
影响因子：
5.7
通讯作者：
Katano, Mitsuo
中科院分区：
文献类型：
--
作者：
Nagai, Shuntaro;Nakamura, Masafumi;Katano, Mitsuo
据报道，刺猬（Hh）信号通路与胰腺癌的生长有关，但其在侵袭性表型中的作用却知之甚少。因此，我们使用Matrigel侵袭测定研究了Hh途径在胰腺癌细胞侵袭中的作用。通过环巴胺阻断Hh通路抑制胰腺癌细胞侵袭，并降低基质金属蛋白酶（MMP）-9的表达。相比之下，通过添加外源性Sonic hedgehog激活Hh通路增加细胞侵袭和MMP-9表达。稳定转染Gli 1的胰腺癌细胞的侵袭性增加，这与MMP-9的活化有关。我们还发现，抑制MMP-9的小干扰RNA阻断了Gli 1转染细胞的侵袭力增加。此外，通过小干扰RNA抑制Gli 1抑制胰腺癌细胞的侵袭性和MMP-9的表达。综上所述，这些发现表明，Hh通路的成员，特别是Gli 1，通过调节MMP-9的表达在胰腺癌细胞的侵袭性中发挥重要作用。
The hedgehog (Hh) signaling pathway has been reported to be associated with the growth of pancreatic cancer, but its role in the invasive phenotype is poorly understood. Therefore, we investigated the role of the Hh pathway in pancreatic cancer cell invasiveness using a Matrigel invasion assay. Blockade of the Hh pathway by cyclopamine inhibited pancreatic cancer cell invasion in association with a decreased expression of matrix metalloproteinase (MMP)-9. By contrast, activation of the Hh pathway by the addition of exogenous Sonic hedgehog increased cell invasion and MMP-9 expression. Stable transfection of pancreatic cancer cells with Gli1 increased their invasiveness, which was associated with activation of MMP-9. We also showed that inhibition of MMP-9 by small interfering RNA blocked the increased invasiveness of Gli1-transfected cells. Furthermore, inhibition of Gli1 by small interfering RNA suppressed the invasiveness and MMP-9 expression of pancreatic cancer cells. Taken together, these findings suggest that members of the Hh pathway, especially Gli1, play an important role in the invasiveness of pancreatic cancer cells through the regulation of MMP-9 expression.