| First Author | Vara-Ciruelos D | Year | 2019 |
| Journal | Cell Rep | Volume | 27 |
| Issue | 3 | Pages | 690-698.e4 |
| PubMed ID | 30995468 | Mgi Jnum | J:281849 |
| Mgi Id | MGI:6380903 | Doi | 10.1016/j.celrep.2019.03.067 |
| Citation | Vara-Ciruelos D, et al. (2019) Phenformin, But Not Metformin, Delays Development of T Cell Acute Lymphoblastic Leukemia/Lymphoma via Cell-Autonomous AMPK Activation. Cell Rep 27(3):690-698.e4 |
| abstractText | AMPK acts downstream of the tumor suppressor LKB1, yet its role in cancer has been controversial. AMPK is activated by biguanides, such as metformin and phenformin, and metformin use in diabetics has been associated with reduced cancer risk. However, whether this is mediated by cell-autonomous AMPK activation within tumor progenitor cells has been unclear. We report that T-cell-specific loss of AMPK-alpha1 caused accelerated growth of T cell acute lymphoblastic leukemia/lymphoma (T-ALL) induced by PTEN loss in thymic T cell progenitors. Oral administration of phenformin, but not metformin, delayed onset and growth of lymphomas, but only when T cells expressed AMPK-alpha1. This differential effect of biguanides correlated with detection of phenformin, but not metformin, in thymus. Phenformin also enhanced apoptosis in T-ALL cells both in vivo and in vitro. Thus, AMPK-alpha1 can be a cell-autonomous tumor suppressor in the context of T-ALL, and phenformin may have potential for the prevention of some cancers. |
