| First Author | Whittle MC | Year | 2015 |
| Journal | Cell | Volume | 161 |
| Issue | 6 | Pages | 1345-60 |
| PubMed ID | 26004068 | Mgi Jnum | J:223403 |
| Mgi Id | MGI:5648776 | Doi | 10.1016/j.cell.2015.04.048 |
| Citation | Whittle MC, et al. (2015) RUNX3 Controls a Metastatic Switch in Pancreatic Ductal Adenocarcinoma. Cell 161(6):1345-60 |
| abstractText | For the majority of patients with pancreas cancer, the high metastatic proclivity is life limiting. Some patients, however, present with and succumb to locally destructive disease. A molecular understanding of these distinct disease manifestations can critically inform patient management. Using genetically engineered mouse models, we show that heterozygous mutation of Dpc4/Smad4 attenuates the metastatic potential of Kras(G12D/+);Trp53(R172H/+) pancreatic ductal adenocarcinomas while increasing their proliferation. Subsequent loss of heterozygosity of Dpc4 restores metastatic competency while further unleashing proliferation, creating a highly lethal combination. Expression levels of Runx3 respond to and combine with Dpc4 status to coordinately regulate the balance between cancer cell division and dissemination. Thus, Runx3 serves as both a tumor suppressor and promoter in slowing proliferation while orchestrating a metastatic program to stimulate cell migration, invasion, and secretion of proteins that favor distant colonization. These findings suggest a model to anticipate likely disease behaviors in patients and tailor treatment strategies accordingly. |
