title: A suppressor of multiple extracellular matrix-degrading proteases and cancer metastasis.
abstract: Cancer metastasis remains the most poorly understood process in cancer biology. It involves the degradation of extracellular matrix (ECM) proteins by a series of 'tumour-associated' proteases. Here we report the identification of a novel protease suppressor, NYD-SP8, which is located on human chromosome 19q13.2. NYD-SP8 encodes a 27 kD GPI-anchored cell surface protein, which shows structural homology to urokinase plasminogen activator receptor (uPAR). Co-immunoprecipitation experiments showed that NYD-SP8 binds to uPA/uPAR complexes and interfere with active uPA production. Overexpression of NYD-SP8 results in reducing activities of the three major classes of proteases known to be involved in ECM degradation, including uPA, matrix metalloproteinases (MMPs) and cathepsin B, leading to suppression of both in vitro and in vivo cancer cell invasion and metastasis. These data demonstrate an important role of NYD-SP8 in regulating ECM degradation, providing a novel mechanism that modulates urokinase signalling in the suppression of cancer progression.
authors.affiliation: Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Lan Lan
authors.initials: LL
authors.lastname: Yin
authors.forename: Chin Man
authors.initials: CM
authors.lastname: Chung
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Kin Lam
authors.initials: KL
authors.lastname: Fok
authors.forename: Chuen Pei
authors.initials: CP
authors.lastname: Ng
authors.forename: Rui Rui
authors.initials: RR
authors.lastname: Jia
authors.forename: Xuan
authors.initials: X
authors.lastname: Ren
authors.forename: Jiannong
authors.initials: J
authors.lastname: Zhou
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Xiao Hang
authors.initials: XH
authors.lastname: Zhao
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.forename: Hu
authors.initials: H
authors.lastname: Zhu
authors.forename: Xiao Hu
authors.initials: XH
authors.lastname: Zhang
authors.forename: Lai Ling
authors.initials: LL
authors.lastname: Tsang
authors.forename: Ye
authors.initials: Y
authors.lastname: Bi
authors.forename: Zuomin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Fugen
authors.initials: F
authors.lastname: Mo
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wong
authors.forename: Yiu Wa
authors.initials: YW
authors.lastname: Chung
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D005109:Extracellular Matrix / Q000201:enzymology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010716:Phosphatidylinositols / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D008565:Membrane Proteins; D010716:Phosphatidylinositols; D011480:Protease Inhibitors; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; C539319:TEX101 protein, human; D002401:Cathepsin B