title: δ-Catenin promotes E-cadherin processing and activates β-catenin-mediated signaling: implications on human prostate cancer progression.
abstract: δ-Catenin binds the juxtamembrane domain of E-cadherin and is known to be overexpressed in some human tumors. However, the functions of δ-catenin in epithelial cells and carcinomas remain elusive. We found that prostate cancer cells overexpressing δ-catenin show an increase in multi-layer growth in culture. In these cells, δ-catenin colocalizes with E-cadherin at the plasma membrane, and the E-cadherin processing is noticeably elevated. E-Cadherin processing induced by δ-catenin is serum-dependent and requires MMP- and PS-1/γ-secretase-mediated activities. A deletion mutant of δ-catenin that deprives the ability of δ-catenin to bind E-cadherin or to recruit PS-1 to E-cadherin totally abolishes the δ-catenin-induced E-cadherin processing and the multi-layer growth of the cells. In addition, prostate cancer cells overexpressing δ-catenin display an elevated total β-catenin level and increase its nuclear distribution, resulting in the activation of β-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 δ-catenin, shows increased β-catenin nuclear localization and more rapid growth rates. Moreover, the metastatic xenograft tumor weights positively correlate with the level of 29kD E-cadherin fragment, and primary human prostate tumor tissues also show elevated levels of δ-catenin expression and the E-cadherin processing. Taken together, these results suggest that δ-catenin plays an important role in prostate cancer progression through inducing E-cadherin processing and thereby activating β-catenin-mediated oncogenic signals.
authors.affiliation: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea.
authors.forename: Hangun
authors.initials: H
authors.lastname: Kim
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: He
authors.forename: Ilhwan
authors.initials: I
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.forename: Yonghee
authors.initials: Y
authors.lastname: Kim
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Seo
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Murnane
authors.forename: Chaeyong
authors.initials: C
authors.lastname: Jung
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Jeong-Joon
authors.initials: JJ
authors.lastname: Min
authors.forename: Dong-Deuk
authors.initials: DD
authors.lastname: Kwon
authors.forename: Kyung Keun
authors.initials: KK
authors.lastname: Kim
authors.forename: Qun
authors.initials: Q
authors.lastname: Lu
authors.forename: Kwonseop
authors.initials: K
authors.lastname: Kim
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins / Q000502:physiology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000473:pathology*; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D051176:beta Catenin; D000095002:Delta Catenin