title: Apoptosis Inhibitor 5 Increases Metastasis via Erk-mediated MMP expression.
abstract: Apoptosis inhibitor 5 (API5) has recently been identified as a tumor metastasis-regulating gene in cervical cancer cells. However, the precise mechanism of action for API5 is poorly understood. Here, we show that API5 increases the metastatic capacity of cervical cancer cells in vitro and in vivo via up-regulation of MMP-9. Interestingly, API5-mediated metastasis was strongly dependent on the Erk signaling pathway. Conversely, knock-down of API5 via siRNA technology decreased the level of phospho-Erk, the activity of the MMPs, in vitro invasion, and in vivo pulmonary metastasis. Moreover, the Erk-mediated metastatic action was abolished by the mutation of leucine into arginine within the heptad leucine repeat region, which affects protein-protein interactions. Thus, API5 increases the metastatic capacity of tumor cells by up-regulating MMP levels via activation of the Erk signaling pathway.
authors.affiliation: Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Ansan 425-707; Department of Biochemistry, Korea University College of Medicine, Seoul 136-705, Korea.
authors.forename: Kwon-Ho
authors.initials: KH
authors.lastname: Song
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience & Biothechnology (KRIBB), Daejeon 305-806, Korea.
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Ansan 425-707; Department of Biochemistry, Korea University College of Medicine, Seoul 136-705, Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Noh
authors.affiliation: Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Ansan 425-707, Korea.
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Bae
authors.affiliation: Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Ansan 425-707, Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Ansan 425-707; Department of Biochemistry, Korea University College of Medicine, Seoul 136-705, Korea.
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience & Biothechnology (KRIBB), Daejeon 305-806, Korea.
authors.forename: Jinhoi
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, Seoul 143-701, Korea.
authors.forename: Tae Heung
authors.initials: TH
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-779, Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Ansan 425-707; Department of Biochemistry, Korea University College of Medicine, Seoul 136-705, Korea.
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: Department of Physiology, Seoul National University, College of Medicine, Seoul 110-779, Korea.
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
authors.affiliation: Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Ansan 425-707; Department of Biochemistry, Korea University College of Medicine, Seoul 136-705, Korea.
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Kim
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000556:secondary*; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*
chemical_list: C108386:API5 protein, human; D051017:Apoptosis Regulatory Proteins; D009687:Nuclear Proteins; D018808:Transcription Factor AP-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9