Mutant cadherin affects epithelial morphogenesis and invasion, but not transformation

Megan L. Troxell, David J. Loftus, W. James Nelson, James A. Marrs

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

MDCK cells were engineered to reversibly express mutant E-cadherin protein with a large extracellular deletion. Mutant cadherin overexpression reduced the expression of endogenous E- and K-cadherins in MDCK cells to negligible levels, resulting in decreased cell adhesion. Despite severe impairment of the cadherin adhesion system, cells overexpressing mutant E-cadherin formed fluid-filled cysts in collagen gel cultures and responded to hepatocyte growth factor/scatter factor (HGF/SF) that induced cellular extension formation with a frequency similar to that of control cysts. However, cells were shed from cyst walls into the lumen and into the collagen matrix prior to and during HGF/SF induced tubule extension. Despite the propensity for cell dissociation, MDCK cells lacking cadherin adhesion molecules were not capable of anchorage-independent growth in soft agar and cell proliferation rate was not affected. Thus, cadherin loss does not induce transformation, despite inducing and invasive phenotype, a later stage of tumor progression. These experiments are especially relevant to tumor progression in cells with altered E-cadherin expression, particularly tumor samples with identified E-cadherin extracellular domain genomic mutations.

Original languageEnglish (US)
Pages (from-to)1237-1246
Number of pages10
JournalJournal of Cell Science
Volume114
Issue number6
StatePublished - Apr 23 2001

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Keywords

  • Cadherin
  • Transformation
  • Tubulogenesis

ASJC Scopus subject areas

  • Cell Biology

Cite this

Troxell, M. L., Loftus, D. J., Nelson, W. J., & Marrs, J. A. (2001). Mutant cadherin affects epithelial morphogenesis and invasion, but not transformation. Journal of Cell Science, 114(6), 1237-1246.