title: TMPRSS4 upregulates uPA gene expression through JNK signaling activation to induce cancer cell invasion.
abstract: TMPRSS4 is a novel type II transmembrane serine protease that is highly expressed in pancreatic, thyroid, colon, and other cancer tissues. Previously, we demonstrated that TMPRSS4 mediates tumor cell invasion, migration, and metastasis. However, the mechanisms by which TMPRSS4 contributes to invasion are not fully understood. Here, we demonstrated that TMPRSS4 induced the transcription of the urokinase-type plasminogen activator (uPA) gene through activating the transcription factors Sp1, Sp3, and AP-1 in mainly a JNK-dependent manner and that the induction of uPA was required for TMPRSS4-mediated cancer cell invasion and signaling events. In addition, the uPA receptor was involved in TMPRSS4-induced signaling activation and subsequent uPA expression probably through its association with TMPRSS4 on the cell surface. Immunohistochemical analysis showed that uPA expression was significantly correlated with TMPRSS4 expression in human lung and prostate cancers. These observations suggest that TMPRSS4 is an important regulator of uPA gene expression; the upregulation of uPA by TMPRSS4 contributes to invasion and may represent a novel mechanism for the control of invasion.
authors: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors: Hye-Jin
authors: HJ
authors: Min
authors: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
authors: Yunhee
authors: Y
authors: Lee
authors: Department of Surgery, Chonnam National University Medical School, Hwasun 519-809, Republic of Korea.
authors: Xue-Feng
authors: XF
authors: Zhao
authors: Department of Surgery, Chonnam National University Medical School, Hwasun 519-809, Republic of Korea.
authors: Young-Kyu
authors: YK
authors: Park
authors: Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors: Myung Kyu
authors: MK
authors: Lee
authors: Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Jung Weon
authors: JW
authors: Lee
authors: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea. Electronic address: semikim@kribb.re.kr.
authors: Semi
authors: S
authors: Kim
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D055293:Receptors, Urokinase Plasminogen Activator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051705:Sp3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D055293:Receptors, Urokinase Plasminogen Activator; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D051705:Sp3 Transcription Factor; D048031:JNK Mitogen-Activated Protein Kinases; D012697:Serine Endopeptidases; C528837:TMPRSS4 protein, human; D014568:Urokinase-Type Plasminogen Activator
keywords: EMT; ERK kinase; ERK1/2; FAK; Invasion; JNK; MAPK; MEK; STAT; TMPRSS4; Transcription; c-Jun N-terminal kinase; epithelial–mesenchymal transition; extracellular signal-regulated kinase 1/2; focal adhesion kinase; mitogen-activated protein kinase; siRNA; signal transducer and activator of transcription; small interfering RNA; uPA; urokinase-type plasminogen activator