PMID- 10597309
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20220224
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 50
DP  - 1999 Nov 25
TI  - Calcium influx triggers the sequential proteolysis of extracellular and
      cytoplasmic domains of E-cadherin, leading to loss of beta-catenin from cell-cell
      contacts.
PG  - 7080-90
AB  - Cadherins are major cell-cell adhesion molecules in both tumor and normal
      tissues. Although serum levels of soluble E-cadherin have been shown to be higher
      in the cancer patients than in healthy volunteers, the detail mechanism
      regulating release of soluble E-cadherin remains to be elucidated. Here we show
      that the ectodomain of E-cadherin is proteolytically cleaved from some cancer
      cells by a membrane-bound metalloprotease to yield soluble form, and the residual
      membrane-tethered cleavage product is subsequently degraded by intracellular
      proteolytic pathway. Futhermore, we show that extracellular calcium influx, that 
      is induced by mechanical scraping of cells or ionomycin treatment, enhances the
      metalloprotease-mediated E-cadherin cleavage and the subsequent degradation of
      the cytoplasmic domain. Immunocytochemical analysis demonstrates that the
      sequential proteolysis of E-cadherin triggered by the calcium influx results in
      translocation of beta-catenin from the cell-cell contacts to cytoplasm. Our data 
      suggest that calcium influx-induced proteolysis of E-cadherin not only disrupts
      the cell-cell adhesion but also activates beta-catenin-mediated intracellular
      signaling pathway, potentially leading to alterations in motility and
      proliferation activity of cells.
FAU - Ito, K
AU  - Ito K
AD  - Department of Tumor Genetics and Biology, Kumamoto University School of Medicine,
      Japan.
FAU - Okamoto, I
AU  - Okamoto I
FAU - Araki, N
AU  - Araki N
FAU - Kawano, Y
AU  - Kawano Y
FAU - Nakao, M
AU  - Nakao M
FAU - Fujiyama, S
AU  - Fujiyama S
FAU - Tomita, K
AU  - Tomita K
FAU - Mimori, T
AU  - Mimori T
FAU - Saya, H
AU  - Saya H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (Membrane Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Base Sequence
MH  - Biological Transport
MH  - Cadherins/*metabolism
MH  - Calcium/*metabolism
MH  - Cytoplasm/metabolism
MH  - Cytoskeletal Proteins/*metabolism
MH  - DNA Primers
MH  - Humans
MH  - Hydrolysis
MH  - Membrane Proteins/metabolism
MH  - Metalloendopeptidases/metabolism
MH  - Protein Processing, Post-Translational
MH  - *Trans-Activators
MH  - Tumor Cells, Cultured
MH  - beta Catenin
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1038/sj.onc.1203191 [doi]
PST - ppublish
SO  - Oncogene. 1999 Nov 25;18(50):7080-90. doi: 10.1038/sj.onc.1203191.