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http://hdl.handle.net/2445/178674
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DC Field | Value | Language |
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dc.contributor.author | Rubio, Teresa | - |
dc.contributor.author | Weyershaeuser, Judith | - |
dc.contributor.author | Montero, Marta G. | - |
dc.contributor.author | Hoffmann, Andreas | - |
dc.contributor.author | Lujan, Pablo | - |
dc.contributor.author | Jechlinger, Martin | - |
dc.contributor.author | Sotillo, Rocio | - |
dc.contributor.author | Köhn, Maja | - |
dc.date.accessioned | 2021-06-25T11:01:22Z | - |
dc.date.available | 2021-06-25T11:01:22Z | - |
dc.date.issued | 2021-06-15 | - |
dc.identifier.uri | http://hdl.handle.net/2445/178674 | - |
dc.description.abstract | Expression of the phosphatase of regenerating liver-3 (PRL-3) is known to promote tumor growth in gastrointestinal adenocarcinomas, and the incidence of tumor formation upon inflammatory events correlates with PRL-3 levels in mouse models. These carcinomas and their onset are associated with the impairment of intestinal cell homeostasis, which is regulated by a balanced number of Paneth cells and Lgr5 expressing intestinal stem cells (Lgr5+ ISCs). Nevertheless, the consequences of PRL-3 overexpression on cellular homeostasis and ISC fitness in vivo are unexplored. Here, we employ a doxycycline-inducible PRL-3 mouse strain to show that aberrant PRL-3 expression within a non-cancerous background leads to the death of Lgr5+ ISCs and to Paneth cell expansion. A higher dose of PRL-3, resulting from homozygous expression, led to mice dying early. A primary 3D intestinal culture model obtained from these mice confirmed the loss of Lgr5+ ISCs upon PRL-3 expression. The impaired intestinal organoid formation was rescued by a PRL inhibitor, providing a functional link to the observed phenotypes. These results demonstrate that elevated PRL-3 phosphatase activity in healthy intestinal epithelium impairs intestinal cell homeostasis, which correlates this cellular mechanism of tumor onset with PRL-3-mediated higher susceptibility to tumor formation upon inflammatory or mutational events.Key messages• Transgenic mice homozygous for PRL-3 overexpression die early.• PRL-3 heterozygous mice display disrupted intestinal self-renewal capacity.• PRL-3 overexpression alone does not induce tumorigenesis in the mouse intestine.• PRL-3 activity leads to the death of Lgr5+ ISCs and Paneth cell expansion.• Impairment of cell homeostasis correlates PRL-3 action with tumor onset mechanisms. | - |
dc.format.extent | 14 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Springer Nature | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1007/s00109-021-02097-9 | - |
dc.relation.ispartof | Journal of Molecular Medicine, 2021 | - |
dc.relation.uri | https://doi.org/10.1007/s00109-021-02097-9 | - |
dc.rights | cc by (c) Rubio et al., 2021 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Càncer | - |
dc.subject.classification | Homeòstasi | - |
dc.subject.other | Cancer | - |
dc.subject.other | Homeostasis | - |
dc.title | The phosphatase PRL-3 affects intestinal homeostasis by altering the crypt cell composition | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2021-06-25T08:20:53Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 34129057 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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Rubio2021_Article_ThePhosphatasePRL-3AffectsInte.pdf | 5.1 MB | Adobe PDF | View/Open |
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