title: STAT3 and ERK Signaling Pathways Are Implicated in the Invasion Activity by Oncostatin M through Induction of Matrix Metalloproteinases 2 and 9.
abstract: OBJECTIVE
  Our previous studies have shown that oncostatin M (OSM) promotes trophoblast invasion activity through increased enzyme activity of matrix metalloproteinase (MMP)-2 and -9. We further investigated OSM-induced intracellular signaling mechanisms associated with these events in the immortalized human trophoblast cell line HTR8/SVneo.
  
  
  METHODS
  We investigated the effects of OSM on RNA and protein expression of MMP-2 and -9 in the first-trimester extravillous trophoblast cell line (HTR8/SVneo) via Western blot. The selective signal transducer and activator of transcription (STAT)3 inhibitor, stattic, STAT3 siRNA, and extracellular signal-regulated kinase (ERK) siRNA were used to investigate STAT3 and ERK activation by OSM. The effects of STAT3 and ERK inhibitors on OSM-induced enzymatic activities of MMP-2 and -9 and invasion activity were further determined via Western blot and gelatin zymography.
  
  
  RESULTS
  OSM-induced MMP-2 and -9 protein expression was significantly suppressed by STAT3 inhibition with stattic and STAT3 siRNA silencing, whereas the ERK1/2 inhibitor (U0126) and ERK silencing significantly suppressed OSM-induced MMP-2 protein expression. OSM-induced MMP-2 and MMP-9 enzymatic activities were significantly decreased by stattic pretreatment. The increased invasion activity induced by OSM was significantly suppressed by STAT3 and ERK1/2 inhibition, though to a greater extent by STAT3 inhibition.
  
  
  CONCLUSIONS
  Both STAT3 and ERK signaling pathways are involved in OSM-induced invasion activity of HTR8/SVneo cells. Activation of STAT3 appears to be critical for the OSM-mediated increase in invasiveness of HTR8/SVneo cells.
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hyun Sun
authors.initials: HS
authors.lastname: Ko
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Byung Joon
authors.initials: BJ
authors.lastname: Park
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sae Kyung
authors.initials: SK
authors.lastname: Choi
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Kang
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Ahyoung
authors.initials: A
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Ho Shik
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: In Yang
authors.initials: IY
authors.lastname: Park
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea. jcshin@catholic.ac.kr.
authors.forename: Jong Chul
authors.initials: JC
authors.lastname: Shin
mesh_terms: D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D053683:Oncostatin M / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053683:Oncostatin M; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Oncostatin M; extracellular signal-regulated kinases (ERK)1/2; signal transducer and activator of transcription (STAT)3; signaling pathway; trophoblasts