Open AccessA suppressor of multiple extracellular matrix‐degrading proteases and cancer metastasis
Author(s) -
Yin Lan lan,
Chung Chin Man,
Chen Jie,
Fok Kin Lam,
Ng Chuen Pei,
Jia Rui Rui,
Ren Xuan,
Zhou Jiang,
Zhang Tong,
Zhao Xiao Hang,
Lin Min,
Zhu Hu,
Zhang Xiao Hu,
Tsang Lai Ling,
Bi Ye,
Zhou Zuomin,
Mo Fugen,
Wong Nathalie,
Chung Yiu Wa,
Sha Jiahao,
Chan Hsiao Chang
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00576.x
Subject(s) - urokinase receptor , proteases , extracellular matrix , cancer cell , metastasis , microbiology and biotechnology , chemistry , cancer research , biology , cancer , biochemistry , receptor , enzyme , genetics
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.