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

Shuntaro Nagai, Masafumi Nakamura, Kosuke Yanai, Junji Wada, Takashi Akiyoshi, Hiroshi Nakashima, Kenoki Ohuchida, Norihiro Sato, Masao Tanaka, Mitsuo Katano

Research output: Contribution to journalArticle

68 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1377-1384
Number of pages8
JournalCancer Science
Volume99
Issue number7
DOIs
Publication statusPublished - Jul 2008

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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