A suppressor of multiple extracellular matrix-degrading proteases and cancer metastasis.
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.
Yin
Lan Lan
LL
Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
Chung
Chin Man
CM
Chen
Jie
J
Fok
Kin Lam
KL
Ng
Chuen Pei
CP
Jia
Rui Rui
RR
Ren
Xuan
X
Zhou
Jiannong
J
Zhang
Tong
T
Zhao
Xiao Hang
XH
Lin
Min
M
Zhu
Hu
H
Zhang
Xiao Hu
XH
Tsang
Lai Ling
LL
Bi
Ye
Y
Zhou
Zuomin
Z
Mo
Fugen
F
Wong
Nathalie
N
Chung
Yiu Wa
YW
Sha
Jiahao
J
Chan
Hsiao Chang
HC
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
D008565:Membrane Proteins; D010716:Phosphatidylinositols; D011480:Protease Inhibitors; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; C539319:TEX101 protein, human; D002401:Cathepsin B