| http://purl.uniprot.org/citations/31259422 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31259422 | http://www.w3.org/2000/01/rdf-schema#comment | "Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of less than 4% and desperately needs novel effective therapeutics. Integrin αvβ6 has been linked with poor prognosis in cancer but its potential as a target in PDAC remains unclear. We report that transcriptional expression analysis revealed that high levels of β6 mRNA correlated strongly with significantly poorer survival (n = 491 cases, p = 3.17 × 10-8 ). In two separate cohorts, we showed that over 80% of PDACs expressed αvβ6 protein and that paired metastases retained αvβ6 expression. In vitro, integrin αvβ6 promoted PDAC cell growth, survival, migration, and invasion. Treatment of both αvβ6-positive human PDAC xenografts and transgenic mice bearing αvβ6-positive PDAC with the αvβ6 blocking antibody 264RAD, combined with gemcitabine, significantly reduced tumour growth (p < 0.0001) and increased survival (log-rank test, p < 0.05). Antibody therapy was associated with suppression of tumour cell activity (suppression of pErk growth signals, increased apoptosis seen as activated caspase-3) and suppression of the pro-tumourigenic microenvironment (suppression of TGFβ signalling, fewer αSMA-positive myofibroblasts, decreased blood vessel density). These data show that αvβ6 promotes PDAC growth through both tumour cell and tumour microenvironment mechanisms and represents a valuable target for PDAC therapy. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.org/dc/terms/identifier | "doi:10.1002/path.5320"xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Bailey P."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Chang D."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Desai A."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Marshall J.F."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Moore K.M."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Scarpa A."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Evans T.J."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Keyse S.M."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Haider S."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Sansom O.J."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Chelala C."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Barry S.T."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Kocher H.M."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Morton J.P."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Jamieson N.B."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Vallath S."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Lawlor R."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Steele C.W."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Biankin A."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Brentnall A."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/author | "Reader C.S."xsd:string |
| http://purl.uniprot.org/citations/31259422 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |