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Fuchs, M.* ; Hutzler, P. ; Brunner, I. ; Schlegel,* ; Mages, J. ; Reuning, U.* ; Hapke, S.* ; Duyster, J.* ; Hirohashi, S.* ; Genda, T.* ; Sakamoto, M.* ; Überall, F.* ; Höfler, H. ; Becker, K.-H. ; Luber, B.*

Motility Enhancement by Tumor-Derived Mutant E-Cadherin is Sensitive to Treatment with Epidermal Growth Factor Receptor and Phosphatidylinositol 3-Kinase Inhibitors.

Exp. Cell Res. 276, 129-141 (2002)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Diffuse-type gastric and lobular breast cancers are characterized by frequent mutations in the cell adhesion molecule E-cadherin. Here we report that tumor-associated mutations of E-cadherin enhanced random cell movement of transfected MDA-MB-435S mammary carcinoma cells as compared to wild-type (wt) E-cadherin-expressing cells. The mutations included in frame deletions of exons 8 or 9 and a point mutation in exon 8 which all affect putative calcium-binding sites within the linker region of the second and third extracellular domain. Motility enhancement by mutant E-cadherin was investigated by time-lapse laser scanning microscopy. Increased cell motility stimulated by mutant E-cadherin was influenced by cell–matrix interactions. The motility-increasing activity of mutant E-cadherin was blocked by application of pharmacological inhibitors of epidermal growth factor receptor and phosphatidylinositol (PI) 3-kinase. Investigation of the activation status of PI 3-kinase and the downstream signaling molecules Akt/protein kinase B and MAP kinase p44/42 showed that these kinases are not more strongly activated in mutant E-cadherin-expressing cells than in wt E-cadherin-expressing cells. Instead, the basal level of PI 3-kinase is necessary for mutant E-cadherin-enhanced cell motility. Our data suggest a critical role of E-cadherin mutations for the fine tuning of tumor cell motility.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords E-cadherin cell mortality EGF receptor PI 3-kinase MAP kinase Akt/protein kinase B.
ISSN (print) / ISBN 1090-2422
e-ISSN 0014-4827
Journal Experimental Cell Research
Quellenangaben Volume: 276, Issue: 2, Pages: 129-141 Article Number: , Supplement: ,
Publisher Academic Press
Publishing Place Orlando, Fla.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Pathology (PATH)