| First Author | Martín-López J | Year | 2018 |
| Journal | Oncotarget | Volume | 9 |
| Issue | 16 | Pages | 12554-12561 |
| PubMed ID | 29560090 | Mgi Jnum | J:320563 |
| Mgi Id | MGI:6874406 | Doi | 10.18632/oncotarget.23792 |
| Citation | Martin-Lopez J, et al. (2018) Mutation of TGFbeta-RII eliminates NSAID cancer chemoprevention. Oncotarget 9(16):12554-12561 |
| abstractText | Non-steroidal anti-inflammatory drugs (NSAIDs) exhibit anti-neoplastic (chemoprevention) activity for sporadic cancers and the hereditary cancer predisposition Lynch syndrome (LS/HNPCC). However, the mechanism of NSAID tumor suppression has remained enigmatic. Defects in the core mismatch repair (MMR) genes MSH2 and MLH1 are the principal drivers of LS/HNPCC. Previous work has demonstrated that the villin-Cre(+/-)Msh2(flox/flox) (VpC-Msh2) mouse is a reliable model for LS/HNPCC intestinal tumorigenesis, which is significantly suppressed by treatment with the NSAID aspirin (ASA) similar to human chemoprevention. Here we show that including a TGFbeta receptor type-II (Tgfbeta-RII) mutation in the VpC-Msh2 mouse (villin-Cre(+/-)Msh2(flox/flox)Tgfbeta-RII(flox/flox) ) completely eliminates NSAID tumor suppression. These results provide strong genetic evidence that TGFbeta signaling and/or effectors participate in NSAID-dependent anti-neoplastic processes and provide fresh avenues for understanding NSAID chemoprevention and resistance. |
