| First Author | Shields MA | Year | 2022 |
| Journal | Cell Rep | Volume | 38 |
| Issue | 9 | Pages | 110441 |
| PubMed ID | 35235808 | Mgi Jnum | J:325480 |
| Mgi Id | MGI:7286264 | Doi | 10.1016/j.celrep.2022.110441 |
| Citation | Shields MA, et al. (2022) Galpha13 loss in Kras/Tp53 mouse model of pancreatic tumorigenesis promotes tumors susceptible to rapamycin. Cell Rep 38(9):110441 |
| abstractText | Galpha13 transduces signals from G-protein-coupled receptors. While Galpha13 functions as a tumor suppressor in lymphomas, it is not known whether Galpha13 is pro-tumorigenic or tumor suppressive in genetically engineered mouse (GEM) models of epithelial cancers. Here, we show that loss of Galpha13 in the Kras/Tp53 (KPC) GEM model promotes well-differentiated tumors and reduces survival. Mechanistically, tumors developing in KPC mice with Galpha13 loss exhibit increased E-cadherin expression and mTOR signaling. Importantly, human pancreatic ductal adenocarcinoma (PDAC) tumors with low Galpha13 expression also exhibit increased E-cadherin expression and mTOR signaling. Treatment with the mTOR inhibitor rapamycin decreases the growth of syngeneic KPC tumors with Galpha13 loss by promoting cell death. This work establishes a tumor-suppressive role of Galpha13 in pancreatic tumorigenesis in the KPC GEM model and suggests targeting mTOR in human PDAC tumors with Galpha13 loss. |
