PMID- 11228167 OWN - NLM STAT- MEDLINE DCOM- 20010705 LR - 20220215 IS - 0021-9533 (Print) IS - 0021-9533 (Linking) VI - 114 IP - Pt 6 DP - 2001 Mar TI - Mutant cadherin affects epithelial morphogenesis and invasion, but not transformation. PG - 1237-46 AB - 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 an 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. FAU - Troxell, M L AU - Troxell ML AD - Department of Molecular and Cellular Physiology, Beckman Center B109, Stanford University School of Medicine, Stanford, CA 94305-5426, USA. FAU - Loftus, D J AU - Loftus DJ FAU - Nelson, W J AU - Nelson WJ FAU - Marrs, J A AU - Marrs JA LA - eng GR - DK-54518/DK/NIDDK NIH HHS/United States GR - EY-11365/EY/NEI NIH HHS/United States GR - GM-07365/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - J Cell Sci JT - Journal of cell science JID - 0052457 RN - 0 (Cadherins) RN - 0 (Gels) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 9002-18-0 (Agar) RN - 9007-34-5 (Collagen) SB - IM MH - Agar MH - Animals MH - Cadherins/*biosynthesis/genetics MH - Cell Aggregation MH - Cell Division MH - Cell Line MH - Collagen MH - Dogs MH - Epithelial Cells/cytology/drug effects/*physiology MH - Gels MH - Gene Expression MH - Hepatocyte Growth Factor/metabolism/pharmacology MH - Humans MH - Morphogenesis MH - Mutagenesis MH - *Transformation, Genetic EDAT- 2001/03/03 10:00 MHDA- 2001/07/06 10:01 CRDT- 2001/03/03 10:00 PHST- 2001/03/03 10:00 [pubmed] PHST- 2001/07/06 10:01 [medline] PHST- 2001/03/03 10:00 [entrez] AID - 10.1242/jcs.114.6.1237 [doi] PST - ppublish SO - J Cell Sci. 2001 Mar;114(Pt 6):1237-46. doi: 10.1242/jcs.114.6.1237.