PMID- 12138162
OWN - NLM
STAT- MEDLINE
DCOM- 20021125
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 41
DP  - 2002 Oct 11
TI  - Proteinase suppression by E-cadherin-mediated cell-cell attachment in 
      premalignant oral keratinocytes.
PG  - 38159-67
AB  - The expression and activity of epithelial proteinases is under stringent control 
      to prevent aberrant hydrolysis of structural proteins and disruption of tissue 
      architecture. E-cadherin-dependent cell-cell adhesion is also important for 
      maintenance of epithelial structural integrity, and loss of E-cadherin expression 
      has been correlated with enhanced invasive potential in multiple tumor models. To 
      address the hypothesis that there is a functional link between E-cadherin and 
      proteinase expression, we have examined the role of E-cadherin in proteinase 
      regulation. By using a calcium switch protocol to manipulate junction assembly, 
      our data demonstrate that initiation of de novo E-cadherin-mediated adhesive 
      contacts suppresses expression of both relative matrix metalloproteinase-9 levels 
      and net urinary-type plasminogen activator activity. E-cadherin-mediated 
      cell-cell adhesion increases both phosphatidylinositol 3'-kinase 
      (PI3-kinase)-dependent AKT phosphorylation and epidermal growth factor 
      receptor-dependent MAPK/ERK activation. Pharmacologic inhibition of the 
      PI3-kinase pathway, but not the epidermal growth factor receptor/MAPK pathway, 
      prevents E-cadherin-mediated suppression of proteinases and delays junction 
      assembly. Moreover, inhibition of junction assembly with a function-blocking 
      anti-E-cadherin antibody stimulates proteinase-dependent Matrigel invasion. As 
      matrix metalloproteinase-9 and urinary-type plasminogen activator potentiate the 
      invasive activity of oral squamous cell carcinoma, these data suggest 
      E-cadherin-mediated signaling through PI3-kinase can regulate the invasive 
      behavior of cells by modulating proteinase secretion.
FAU - Munshi, Hidayatullah G
AU  - Munshi HG
AD  - Division of Hematology/Oncology, Department of Medicine, Feinberg School of 
      Medicine and the Robert H. Lurie Comprehensive Cancer Center of Northwestern 
      University, Chicago, Illinois 60611, USA.
FAU - Ghosh, Supurna
AU  - Ghosh S
FAU - Mukhopadhyay, Subhendu
AU  - Mukhopadhyay S
FAU - Wu, Yi I
AU  - Wu YI
FAU - Sen, Ratna
AU  - Sen R
FAU - Green, Kathleen J
AU  - Green KJ
FAU - Stack, M Sharon
AU  - Stack MS
LA  - eng
GR  - DE12328/DE/NIDCR NIH HHS/United States
GR  - R01 CA 85870/CA/NCI NIH HHS/United States
GR  - T32 CA79447/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020723
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cadherins)
RN  - 0 (Chelating Agents)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 526U7A2651 (Egtazic Acid)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.- (Endopeptidases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Cadherins/*metabolism
MH  - Calcium/metabolism
MH  - Cell Adhesion/*physiology
MH  - Cell Line
MH  - Chelating Agents/metabolism
MH  - Egtazic Acid/metabolism
MH  - Endopeptidases/*metabolism
MH  - ErbB Receptors/metabolism
MH  - Humans
MH  - Keratinocytes/cytology/*metabolism/pathology
MH  - MAP Kinase Signaling System/physiology
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Mouth Mucosa/*cytology/pathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Plasminogen Activator Inhibitor 1/metabolism
MH  - Protease Inhibitors/metabolism
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Tissue Inhibitor of Metalloproteinase-1/metabolism
EDAT- 2002/07/26 10:00
MHDA- 2002/11/26 04:00
CRDT- 2002/07/26 10:00
PHST- 2002/07/26 10:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/07/26 10:00 [entrez]
AID - S0021-9258(18)36292-6 [pii]
AID - 10.1074/jbc.M202384200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Oct 11;277(41):38159-67. doi: 10.1074/jbc.M202384200. Epub 2002 
      Jul 23.