期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1822, 期 4, 页码 509-521出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2011.12.015
关键词
Prostate cancer; Catenin; LEF-1; E-cadherin; Androgen receptor; Wnt
资金
- Korea Healthcare Technology RD project [A101474]
- Ministry for Health, Welfare Family Affairs
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2010-0022501, 2011-0003787]
- Republic of Korea
- NIH/NCI [R01CA111891]
- Department of Defense [K040569]
- Korea Health Promotion Institute [A101474] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Council of Science & Technology (NST), Republic of Korea [E32200] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2009-0065189, 2010-0022501] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
delta-Catenin binds the juxtamembrane domain of E-cadherin and is known to be overexpressed in some human tumors. However, the functions of delta-catenin in epithelial cells and carcinomas remain elusive. We found that prostate cancer cells overexpressing delta-catenin show an increase in multi-layer growth in culture. In these cells, delta-catenin colocalizes with E-cadherin at the plasma membrane, and the E-cadherin processing is noticeably elevated. E-Cadherin processing induced by delta-catenin is serum-dependent and requires MMP- and PS-1/gamma-secretase-mediated activities. A deletion mutant of delta-catenin that deprives the ability of delta-catenin to bind E-cadherin or to recruit PS-1 to E-cadherin totally abolishes the delta-catenin-induced E-cadherin processing and the multi-layer growth of the cells. In addition, prostate cancer cells overexpressing delta-catenin display an elevated total p-catenin level and increase its nuclear distribution, resulting in the activation of beta-catenin/LEF-1-mediated transcription and their downstream target genes as well as androgen receptor-mediated transcription. Indeed, human prostate tumor xenograft in nude mice, which is derived from cells overexpressing delta-catenin, shows increased beta-catenin nuclear localization and more rapid growth rates. Moreover, the metastatic xenograft tumor weights positively correlate with the level of 29 kD E-cadherin fragment, and primary human prostate tumor tissues also show elevated levels of delta-catenin expression and the E-cadherin processing. Taken together, these results suggest that delta-catenin plays an important role in prostate cancer progression through inducing E-cadherin processing and thereby activating beta-catenin-mediated oncogenic signals. (C) 2012 Elsevier B.V. All rights reserved.
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