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Cited by 152Cell Adhesion Molecules ResearchCell death mechanisms and regulationCellular Mechanics and Interactions

Cell-Cell Contacts Prevent Anoikis in Primary Human Colonic Epithelial Cells

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Hofmann, Claudia, Obermeier, Florian, Artinger, Monika, Hausmann, Martin, Falk, Werner, Schoelmerich, Juergen, Rogler, Gerhard, Grossmann, Johannes·2007·Gastroenterology
DOI 10.1053/j.gastro.2006.11.017
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Abstract

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.

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  • The ROCK inhibitor Y27632 prevents cell-cell interaction-dependent anoikis.

    “Thus, we supplemented these cultures with the ROCK inhibitor (Y27632), which prevents cell–cell interaction-dependent anoikis21.”

    From Blimp1+ cells generate functional mouse sebaceous gland organoids in vitro (2019) · cites this paper as [21]

    The Inhibition of Signaling Pathways section lists the inhibitors tested, but does not include Y27632 or a ROCK inhibitor. The Discussion describes cell-cell contacts preventing anoikis in colonic epithelial cells, but does not address whether Y27632 prevents anoikis. Searches for Y27632, ROCK inhibition, and cell-cell interaction-dependent anoikis found no supporting passage in our copy. (LLM, conf=0.76)

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Authors
Hofmann, C., Obermeier, F., Artinger, M., Hausmann, M., Falk, W., Schoelmerich, J., Rogler, G., & Grossmann, J.
Affiliations
  • University of Regensburg (DE)
  • Evangelisches Krankenhaus Bethesda Mönchengladbach (DE)
Corresponding author
Rogler, Gerhard
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2007-02
Volume
132
Issue
2
Pages
587-600
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2006.11.017
OpenAlex
W2095938297
Cited by
152
References
1
Citations by year
2026: 3 · 2025: 3 · 2024: 10 · 2023: 5 · 2022: 4 · 2021: 15 · 2020: 9 · 2019: 10 · 2018: 5 · 2017: 3 · 2016: 7 · 2015: 3 · 2014: 7 · 2013: 9 · 2012: 7
FWCI
5.93
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
anoikis, cell-cell contact, colonic epithelial cells, apoptosis, cell survival signaling, β-catenin, Akt signaling, Src signaling, PI3K/Akt signaling, MEK/ERK1/2 pathway, epidermal growth factor receptor, focal adhesion kinase, cell-matrix adhesion, caspase activation
MeSH terms
Cell Aggregation, Cell Communication, Cell Survival, Epithelial Cells, Humans, Intestinal Mucosa, Phosphorylation, Time Factors, Signal Transduction, Cadherins, src-Family Kinases, Phosphatidylinositol 3-Kinases, Caspases, Anoikis, Extracellular Signal-Regulated MAP Kinases, Cell Shape, Proto-Oncogene Proteins c-akt, beta Catenin, Focal Adhesion Kinase 1, DNA Fragmentation, ErbB Receptors, In Vitro Techniques

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