Hofmann, Claudia and Obermeier, Florian and Artinger, Monika and Hausmann, Martin and Falk, Werner and Schoelmerich, Juergen and Rogler, Gerhard and Grossmann, Johannes (2007) Cell-cell contacts prevent anoikis in primary human colonic epithelial cells. GASTROENTEROLOGY, 132 (2). pp. 587-600. ISSN 0016-5085, 1528-0012
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Background & Aims: Colonic epithelial cells (CECs) receive important survival signals from the extracellular matrix and undergo detachment-induced apoptosis (anoikis) as soon as they lose their cell-matrix anchorage. In contrast to the established role of cell-matrix contact, the role of cell-cell contacts as a physiologic survival factor for CECs is less clear. Methods: Intact CEC crypts gently centrifuged to form a cell aggregate in which cell-cell contacts were maintained. Induction of apoptosis was assessed by Western Blot analysis, colorimetric assays, DNA electrophoresis, 4',6-diamidino-2-phenylindole staining, and flow cytometry. Activation of survival pathways was analyzed by Western blot. The role of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (Erk)1/2, epidermal growth factor receptor, phosphatidylinositol 3-kinase (PI3-K), and Src signaling was investigated using specific inhibitors. Results: Despite a complete loss of cell-matrix adhesion after CEC isolation, activation of caspases was blocked and anoikis was prevented when cell-cell contacts were preserved. CECs with preserved cell-cell contacts exhibited a rapid dephosphorylation of focal adhesion kinase. Aggregated CECs had stable levels of active beta-catenin and phosphorylated Akt, Erk1/2, and epidermal growth factor receptor, but CECs undergoing anoikis rapidly degraded beta-catenin and dephosphorylated Akt. Inhibition of Src- and PI3-K-dependent signaling reversed the antiapoptotic effect of cell-cell contact preservation, while inhibition of the MEK pathway had no effect. Conclusions: integrity of cell-cell contacts compensates for the loss of cell-matrix contact-mediated survival signals in CECs and prevents apoptosis. Cell-cell contact-triggered CEC survival involves antiapoptotic signaling through beta-catenin-, Src-, and PI3-K/Akt- but not through MEK- and focal adhesion kinase-dependent pathways.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; PROTEIN-KINASE B/AKT; INDUCED APOPTOSIS-ANOIKIS; FOCAL ADHESION KINASE; E-CADHERIN; PHOSPHATIDYLINOSITOL 3-KINASE; ULCERATIVE-COLITIS; PHOSPHOINOSITIDE 3-KINASE; TYROSINE PHOSPHORYLATION; DIFFERENTIAL EXPRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Dec 2020 12:06 |
| Last Modified: | 22 Dec 2020 12:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33226 |
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