| http://purl.uniprot.org/citations/34129057 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34129057 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://purl.org/dc/terms/identifier | "doi:10.1007/s00109-021-02097-9"xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://purl.uniprot.org/core/author | "Hoffmann A."xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://purl.uniprot.org/core/author | "Sotillo R."xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://purl.uniprot.org/core/author | "Kohn M."xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://purl.uniprot.org/core/author | "Jechlinger M."xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://purl.uniprot.org/core/author | "Rubio T."xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://purl.uniprot.org/core/author | "Lujan P."xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://purl.uniprot.org/core/author | "Weyershaeuser J."xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://purl.uniprot.org/core/author | "Montero M.G."xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34129057 | http://purl.uniprot.org/core/name | "J Mol Med (Berl)"xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://purl.uniprot.org/core/pages | "1413-1426"xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://purl.uniprot.org/core/title | "The phosphatase PRL-3 affects intestinal homeostasis by altering the crypt cell composition."xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://purl.uniprot.org/core/volume | "99"xsd:string |
| http://purl.uniprot.org/citations/34129057 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34129057 |
| http://purl.uniprot.org/citations/34129057 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34129057 |
| http://purl.uniprot.org/uniprot/#_E9PXS4-mappedCitation-34129057 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34129057 |
| http://purl.uniprot.org/uniprot/#_Q4FK37-mappedCitation-34129057 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34129057 |
| http://purl.uniprot.org/uniprot/#_O75365-mappedCitation-34129057 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34129057 |
| http://purl.uniprot.org/uniprot/#_Q9D658-mappedCitation-34129057 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34129057 |
| http://purl.uniprot.org/uniprot/O75365 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34129057 |
| http://purl.uniprot.org/uniprot/E9PXS4 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34129057 |
| http://purl.uniprot.org/uniprot/Q4FK37 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34129057 |