| http://purl.uniprot.org/citations/25092896 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25092896 | http://www.w3.org/2000/01/rdf-schema#comment | "Triple-negative breast cancer (TNBC) is an aggressive disease subtype that, unlike other subtypes, lacks an effective targeted therapy. Inhibitors of the insulin-like growth factor receptor (IGF1R) have been considered for use in treating TNBC. Here, we provide genetic evidence that IGF1R inhibition promotes development of Wnt1-mediated murine mammary tumors that offer a model of TNBC. We found that in a double transgenic mouse model carrying activated Wnt1 and mutant Igf1r, a reduction in IGF1R signaling reduced tumor latency and promoted more aggressive phenotypes. These tumors displayed a squamous phenotype with increased expression of keratins 5/6 and β-catenin. Notably, cell lineage analyses revealed an increase in basal (CD29(hi)/CD24(+)) and luminal (CD24(+)/CD61+/CD29(lo)) progenitor cell populations, along with increased Nanog expression and decreased Elf5 expression. In these doubly transgenic mice, lung metastases developed with characteristics of the primary tumors, unlike MMTV-Wnt1 mice. Mechanistic investigations showed that pharmacologic inhibition of the IGF1R in vitro was sufficient to increase the tumorsphere-forming efficiency ofMMTV-Wnt1 tumor cells. Tumors from doubly transgenic mice also exhibited an increase in the expression ratio of the IGF-II-sensitive, A isoform of the insulin receptor versus the IR-B isoform, which when stimulated in vitro resulted in enhanced expression of β-catenin. Overall, our results revealed that in Wnt-driven tumors, an attenuation of IGF1R signaling accelerates tumorigenesis and promotes more aggressive phenotypes with potential implications for understanding TNBC pathobiology and treatment."xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-14-0970"xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/author | "Wood T.L."xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/author | "Shin M.E."xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/author | "LeRoith D."xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/author | "Lazzarino D.A."xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/author | "Albanito L."xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/author | "Shushanov S."xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/author | "Gallagher E.J."xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/author | "Goyeneche C.L."xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/author | "Rota L.M."xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/name | "Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/pages | "5668-5679"xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/title | "IGF1R inhibition in mammary epithelia promotes canonical Wnt signaling and Wnt1-driven tumors."xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://purl.uniprot.org/core/volume | "74"xsd:string |
| http://purl.uniprot.org/citations/25092896 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25092896 |
| http://purl.uniprot.org/citations/25092896 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25092896 |
| http://purl.uniprot.org/uniprot/#_E9QNX9-mappedCitation-25092896 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25092896 |
| http://purl.uniprot.org/uniprot/#_Q3UVJ3-mappedCitation-25092896 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25092896 |
| http://purl.uniprot.org/uniprot/#_Q3UR96-mappedCitation-25092896 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25092896 |
| http://purl.uniprot.org/uniprot/#_P04426-mappedCitation-25092896 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25092896 |
| http://purl.uniprot.org/uniprot/#_Q60751-mappedCitation-25092896 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25092896 |
| http://purl.uniprot.org/uniprot/#_Q3U1L4-mappedCitation-25092896 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25092896 |