| http://purl.uniprot.org/citations/23696648 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23696648 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23696648 | http://www.w3.org/2000/01/rdf-schema#comment | "Insulin-like growth factor-1 (IGF1) is a major therapeutic target for cancer. We recently reported that IGF1 directly binds to integrins (αvβ3 and α6β4) and induces ternary complex formation (integrin-IGF1-IGF1 receptor (IGF1R)) and that the integrin binding-defective mutant of IGF1 (R36E/R37E) is defective in signaling and ternary complex formation. These findings predict that R36E/R37E competes with WT IGF1 for binding to IGF1R and inhibits IGF signaling. Here, we described that excess R36E/R37E suppressed cell viability increased by WT IGF1 in vitro in non-transformed cells. We studied the effect of R36E/R37E on viability and tumorigenesis in cancer cell lines. We did not detect an effect of WT IGF1 or R36E/R37E in cancer cells under anchorage-dependent conditions. However, under anchorage-independent conditions, WT IGF1 enhanced cell viability and induced signals, whereas R36E/R37E did not. Notably, excess R36E/R37E suppressed cell viability and signaling induced by WT IGF1 under anchorage-independent conditions. Using cancer cells stably expressing WT IGF1 or R36E/R37E, we determined that R36E/R37E suppressed tumorigenesis in vivo, whereas WT IGF1 markedly enhanced it. R36E/R37E suppressed the binding of WT IGF1 to the cell surface and the subsequent ternary complex formation induced by WT IGF1. R36E/R37E suppressed activation of IGF1R by insulin. WT IGF1, but not R36E/R37E, induced ternary complex formation with the IGF1R/insulin receptor hybrid. These findings suggest that 1) IGF1 induces signals under anchorage-independent conditions and that 2) R36E/R37E acts as a dominant-negative inhibitor of IGF1R (IGF1 decoy). Our results are consistent with a model in which ternary complex formation is critical for IGF signaling."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m113.470872"xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m113.470872"xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Fujita M."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Fujita M."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Wu M."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Wu M."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Wilkerson C."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Wilkerson C."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Takada Y."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Takada Y."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Wilson M.D."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Wilson M.D."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Cardiff R.D."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Cardiff R.D."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Chen J.Q."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Chen J.Q."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Lo S.H."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Lo S.H."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Cedano-Prieto D.M."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Cedano-Prieto D.M."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Takada Y.K."xsd:string |
| http://purl.uniprot.org/citations/23696648 | http://purl.uniprot.org/core/author | "Takada Y.K."xsd:string |