title: Gli1 contributes to the invasiveness of pancreatic cancer through matrix metalloproteinase-9 activation.
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.
authors.affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Nagai
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yanai
authors.forename: Junji
authors.initials: J
authors.lastname: Wada
authors.forename: Takashi
authors.initials: T
authors.lastname: Akiyoshi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakashima
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sato
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
mesh_terms: D045744:Cell Line, Tumor; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000502:physiology*; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D053583:Interleukin-1beta; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9