Birgitta E. Michels, Mohammed Hossameldin Mosa, Britta Moyo Grebbin, Diego Yepes, Tahmineh Darvishi, Johannes Hausmann, Henning Urlaub, Stefan Zeuzem, Hans Michael Kvasnicka, Thomas Oellerich, Henner Farin
- Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as main driver of colorectal cancer (CRC). Targeting Wnt signaling has proven difficult because the pathway is crucial for homeostasis and stem cell renewal. To distinguish oncogenic from physiological Wnt activity, we have performed transcriptome and proteome profiling in isogenic human colon organoids. Culture in the presence or absence of exogenous ligand allowed us to discriminate receptor-mediated signaling from the effects of CRISPR/Cas9-induced APC loss. We could catalog two nonoverlapping molecular signatures that were stable at distinct levels of stimulation. Newly identified markers for normal stem/progenitor cells and adenomas were validated by immunohistochemistry and flow cytometry. We found that oncogenic Wnt signals are associated with good prognosis in tumors of the consensus molecular subtype 2 (CMS2). In contrast, receptor-mediated signaling was linked to CMS4 tumors and poor prognosis. Together, our data represent a valuable resource for biomarkers that allow more precise stratification of Wnt responses in CRC.
Metadaten| Verfasserangaben: | Birgitta E. MichelsORCiDGND, Mohammed Hossameldin MosaORCiDGND, Britta Moyo GrebbinORCiDGND, Diego Yepes, Tahmineh Darvishi, Johannes HausmannORCiDGND, Henning UrlaubORCiD, Stefan ZeuzemORCiDGND, Hans Michael KvasnickaORCiD, Thomas OellerichORCiD, Henner FarinORCiDGND |
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| URN: | urn:nbn:de:hebis:30:3-544866 |
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| DOI: | https://doi.org/10.1084/jem.20180823 |
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| ISSN: | 1540-9538 |
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| ISSN: | 1540-9358 |
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| Pubmed-Id: | https://pubmed.ncbi.nlm.nih.gov/30792186 |
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| Titel des übergeordneten Werkes (Englisch): | Journal of experimental medicine |
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| Verlag: | Rockefeller Univ. Press |
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| Verlagsort: | New York, NY |
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| Dokumentart: | Wissenschaftlicher Artikel |
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| Sprache: | Englisch |
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| Jahr der Fertigstellung: | 2019 |
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| Datum der Erstveröffentlichung: | 21.02.2019 |
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| Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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| Datum der Freischaltung: | 18.05.2020 |
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| Jahrgang: | 216 |
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| Ausgabe / Heft: | 3 |
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| Seitenzahl: | 17 |
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| Erste Seite: | 704 |
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| Letzte Seite: | 720 |
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| Bemerkung: | © 2019 Michels et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
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| HeBIS-PPN: | 465980627 |
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| Institute: | Biowissenschaften / Biowissenschaften |
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| Medizin / Medizin |
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| Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus |
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| DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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| Sammlungen: | Universitätspublikationen |
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| Lizenz (Deutsch): |  Creative Commons - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen |
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Creative Commons - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen