| First Author | Hezel AF | Year | 2012 |
| Journal | Cancer Res | Volume | 72 |
| Issue | 18 | Pages | 4840-5 |
| PubMed ID | 22787119 | Mgi Jnum | J:191017 |
| Mgi Id | MGI:5451157 | Doi | 10.1158/0008-5472.CAN-12-0634 |
| Citation | Hezel AF, et al. (2012) TGF-beta and alphavbeta6 integrin act in a common pathway to suppress pancreatic cancer progression. Cancer Res 72(18):4840-5 |
| abstractText | The TGF-beta pathway is under active consideration as a cancer drug target based on its capacity to promote cancer cell invasion and to create a protumorigenic microenvironment. However, the clinical application of TGF-beta inhibitors remains uncertain as genetic studies show a tumor suppressor function of TGF-beta in pancreatic cancer and other epithelial malignancies. Here, we used genetically engineered mouse models to investigate the therapeutic impact of global TGF-beta inhibition in pancreatic cancer in relation to tumor stage, genetic profile, and concurrent chemotherapy. We found that alphavbeta6 integrin acted as a key upstream activator of TGF-beta in evolving pancreatic cancers. In addition, TGF-beta or alphavbeta6 blockade increased tumor cell proliferation and accelerated both early and later disease stages. These effects were dependent on the presence of Smad4, a central mediator of TGF-beta signaling. Therefore, our findings indicate that alphavbeta6 and TGF-beta act in a common tumor suppressor pathway whose pharmacologic inactivation promotes pancreatic cancer progression. |
