Loss of E-cadherin-mediated cell-cell contacts activates a novel mechanism for up-regulation of the proto-oncogene c-Jun

Loss of E-cadherin-mediated cell-cell contacts can elicit a signaling pathway that leads to acquisition of an invasive phenotype. Here, we show that at the receiving end of this pathway is the proto-oncogene c-Jun, a member of the activator protein-1 family of transcription factors that play a key r...

Full description

Saved in:
Bibliographic Details
Published in:Molecular biology of the cell 2009-04, Vol.20 (7), p.2121-2129
Main Authors: Knirsh, Revital, Ben-Dror, Iris, Spangler, Barbara, Matthews, Gideon D, Kuphal, Silke, Bosserhoff, Anja K, Vardimon, Lily
Format: Article
Language:English
Subjects:
Animals
Cadherins - metabolism
Cell Communication
Cell Line
Chickens
Cytoskeleton - metabolism
Humans
Mice
Mitogen-Activated Protein Kinases - metabolism
Protein Biosynthesis
Proto-Oncogene Proteins c-jun - genetics
Proto-Oncogene Proteins c-jun - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Transcription, Genetic
Up-Regulation - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Loss of E-cadherin-mediated cell-cell contacts can elicit a signaling pathway that leads to acquisition of an invasive phenotype. Here, we show that at the receiving end of this pathway is the proto-oncogene c-Jun, a member of the activator protein-1 family of transcription factors that play a key role in stimulation of cell proliferation and tumor promotion. Cell separation or abrogation of E-cadherin-mediated cell-cell contacts both cause a dramatic increase in accumulation of the c-Jun protein. Unlike growth factors that enhance the expression of c-Jun by activating the transcription of the c-jun gene, the cell contact-dependent increase in c-Jun accumulation is not accompanied by a corresponding increase in c-Jun mRNA or c-Jun protein stability but rather in the translatability of the c-Jun transcript. Consistently, the increase in c-Jun accumulation is not dependent on activation of the mitogen-activated protein kinase or beta-catenin pathways but is mediated by signals triggered by the restructured cytoskeleton. Depolymerization of the cytoskeleton can mimic the effect of cell separation and cause a dramatic increase in c-Jun accumulation, whereas Taxol inhibits the cell contact-dependent increase. This novel mechanism of c-Jun regulation seems to underlie the robust overexpression of c-Jun in tumor cells of patients with colon carcinoma.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E08-12-1196