Gli1 contributes to the invasiveness of pancreatic cancer through matrix metalloproteinase-9 activation

Cancer Science
Shuntaro NagaiMitsuo Katano

Abstract

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.

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Citations

Oct 29, 2009·Cancer Immunology, Immunotherapy : CII·Akio YamasakiMitsuo Katano
Mar 12, 2009·Medical Oncology·Inès ZidiNidhal Ben Amor
Dec 16, 2011·Journal of Gastroenterology·Masafumi NakamuraHidechika Okada
Feb 5, 2011·The Journal of Nutritional Biochemistry·Yang LiJia-Ren Liu
Jun 18, 2011·Cancer Science·Hideya Onishi, Mitsuo Katano
Jan 21, 2014·Cancer Science·Shojiro MatsushitaMitsuo Katano
May 28, 2013·Biochemical and Biophysical Research Communications·Hideya OnishiMitsuo Katano
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May 21, 2020·Diagnostic Pathology·Wenbo QiYanhua Xuan
May 3, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Do Luong HuynhDong Kee Jeong

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