Knirsh, Revital and Ben-Dror, Iris and Spangler, Barbara and Matthews, Gideon D. and Kuphal, Silke and Bosserhoff, Anja K. and Vardimon, Lily (2009) Loss of E-Cadherin-mediated Cell-Cell Contacts Activates a Novel Mechanism for Up-Regulation of the Proto-Oncogene c-Jun. MOLECULAR BIOLOGY OF THE CELL, 20 (7). pp. 2121-2129. ISSN 1059-1524, 1939-4586
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLUCOCORTICOID-RECEPTOR; PROTEIN-KINASES; MESSENGER-RNAS; EXPRESSION; INVASION; ADHESION; AP-1; PHOSPHORYLATION; MICROTUBULES; CARCINOMA; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Sep 2020 14:57 |
| Last Modified: | 18 Sep 2020 14:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29201 |
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