N-cadherin extracellular repeat 4 mediates epithelial to mesenchymal transition and increased motility

J. B. Kim, S. Islam, Y. J. Kim, R. S. Prudoff, K. M. Sass, M. J. Wheelock, K. R. Johnson

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

E- and N-cadherin are members of the classical cadherin family of proteins. E-cadherin plays an important role in maintaining the normal phenotype of epithelial cells. Previous studies from our laboratory and other laboratories have shown that inappropriate expression of N-cadherin by tumor cells derived from epithelial tissue results in conversion of the cell to a more fibroblast-like cell, with increased motility and invasion. Our present study was designed to determine which domains of N-cadherin make it different from E-cadherin, with respect to altering cellular behavior, such as which domains are responsible for the epithelial to mesenchymal transition and increased cell motility and invasion. To address this question, we constructed chimeric cadherins comprised of selected domains of E- and N-cadherin. The chimeras were transfected into epithelial cells to determine their effect on cell morphology and cellular behavior. We found that a 69-amino acid portion of EC-4 of N-cadherin was necessary and sufficient to promote both an epithelial to mesenchymal transition in squamous epithelial cells and increased cell motility. Here, we show that different cadherin family members promote different cellular behaviors. In addition, we identify a novel activity that can be ascribed to the extracellular domain of N-cadherin.

Original languageEnglish (US)
Pages (from-to)1193-1205
Number of pages13
JournalJournal of Cell Biology
Volume151
Issue number6
DOIs
StatePublished - Dec 11 2000

Fingerprint

Epithelial-Mesenchymal Transition
Cadherins
Epithelial Cells
Cell Movement
Epithelium
Fibroblasts
Phenotype

Keywords

  • Cancer
  • E-cadherin
  • Invasion
  • Motility
  • N-cadherin

ASJC Scopus subject areas

  • Cell Biology

Cite this

N-cadherin extracellular repeat 4 mediates epithelial to mesenchymal transition and increased motility. / Kim, J. B.; Islam, S.; Kim, Y. J.; Prudoff, R. S.; Sass, K. M.; Wheelock, M. J.; Johnson, K. R.

In: Journal of Cell Biology, Vol. 151, No. 6, 11.12.2000, p. 1193-1205.

Research output: Contribution to journalArticle

Kim, J. B. ; Islam, S. ; Kim, Y. J. ; Prudoff, R. S. ; Sass, K. M. ; Wheelock, M. J. ; Johnson, K. R. / N-cadherin extracellular repeat 4 mediates epithelial to mesenchymal transition and increased motility. In: Journal of Cell Biology. 2000 ; Vol. 151, No. 6. pp. 1193-1205.
@article{1d4ea7c11f3d4e2ebe291fa09275dcac,
title = "N-cadherin extracellular repeat 4 mediates epithelial to mesenchymal transition and increased motility",
abstract = "E- and N-cadherin are members of the classical cadherin family of proteins. E-cadherin plays an important role in maintaining the normal phenotype of epithelial cells. Previous studies from our laboratory and other laboratories have shown that inappropriate expression of N-cadherin by tumor cells derived from epithelial tissue results in conversion of the cell to a more fibroblast-like cell, with increased motility and invasion. Our present study was designed to determine which domains of N-cadherin make it different from E-cadherin, with respect to altering cellular behavior, such as which domains are responsible for the epithelial to mesenchymal transition and increased cell motility and invasion. To address this question, we constructed chimeric cadherins comprised of selected domains of E- and N-cadherin. The chimeras were transfected into epithelial cells to determine their effect on cell morphology and cellular behavior. We found that a 69-amino acid portion of EC-4 of N-cadherin was necessary and sufficient to promote both an epithelial to mesenchymal transition in squamous epithelial cells and increased cell motility. Here, we show that different cadherin family members promote different cellular behaviors. In addition, we identify a novel activity that can be ascribed to the extracellular domain of N-cadherin.",
keywords = "Cancer, E-cadherin, Invasion, Motility, N-cadherin",
author = "Kim, {J. B.} and S. Islam and Kim, {Y. J.} and Prudoff, {R. S.} and Sass, {K. M.} and Wheelock, {M. J.} and Johnson, {K. R.}",
year = "2000",
month = "12",
day = "11",
doi = "10.1083/jcb.151.6.1193",
language = "English (US)",
volume = "151",
pages = "1193--1205",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "6",

}

TY - JOUR

T1 - N-cadherin extracellular repeat 4 mediates epithelial to mesenchymal transition and increased motility

AU - Kim, J. B.

AU - Islam, S.

AU - Kim, Y. J.

AU - Prudoff, R. S.

AU - Sass, K. M.

AU - Wheelock, M. J.

AU - Johnson, K. R.

PY - 2000/12/11

Y1 - 2000/12/11

N2 - E- and N-cadherin are members of the classical cadherin family of proteins. E-cadherin plays an important role in maintaining the normal phenotype of epithelial cells. Previous studies from our laboratory and other laboratories have shown that inappropriate expression of N-cadherin by tumor cells derived from epithelial tissue results in conversion of the cell to a more fibroblast-like cell, with increased motility and invasion. Our present study was designed to determine which domains of N-cadherin make it different from E-cadherin, with respect to altering cellular behavior, such as which domains are responsible for the epithelial to mesenchymal transition and increased cell motility and invasion. To address this question, we constructed chimeric cadherins comprised of selected domains of E- and N-cadherin. The chimeras were transfected into epithelial cells to determine their effect on cell morphology and cellular behavior. We found that a 69-amino acid portion of EC-4 of N-cadherin was necessary and sufficient to promote both an epithelial to mesenchymal transition in squamous epithelial cells and increased cell motility. Here, we show that different cadherin family members promote different cellular behaviors. In addition, we identify a novel activity that can be ascribed to the extracellular domain of N-cadherin.

AB - E- and N-cadherin are members of the classical cadherin family of proteins. E-cadherin plays an important role in maintaining the normal phenotype of epithelial cells. Previous studies from our laboratory and other laboratories have shown that inappropriate expression of N-cadherin by tumor cells derived from epithelial tissue results in conversion of the cell to a more fibroblast-like cell, with increased motility and invasion. Our present study was designed to determine which domains of N-cadherin make it different from E-cadherin, with respect to altering cellular behavior, such as which domains are responsible for the epithelial to mesenchymal transition and increased cell motility and invasion. To address this question, we constructed chimeric cadherins comprised of selected domains of E- and N-cadherin. The chimeras were transfected into epithelial cells to determine their effect on cell morphology and cellular behavior. We found that a 69-amino acid portion of EC-4 of N-cadherin was necessary and sufficient to promote both an epithelial to mesenchymal transition in squamous epithelial cells and increased cell motility. Here, we show that different cadherin family members promote different cellular behaviors. In addition, we identify a novel activity that can be ascribed to the extracellular domain of N-cadherin.

KW - Cancer

KW - E-cadherin

KW - Invasion

KW - Motility

KW - N-cadherin

UR - http://www.scopus.com/inward/record.url?scp=0034638833&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034638833&partnerID=8YFLogxK

U2 - 10.1083/jcb.151.6.1193

DO - 10.1083/jcb.151.6.1193

M3 - Article

C2 - 11121435

AN - SCOPUS:0034638833

VL - 151

SP - 1193

EP - 1205

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 6

ER -