| First Author | Ripoche D | Year | 2015 |
| Journal | Mol Cell Biol | Volume | 36 |
| Issue | 5 | Pages | 756-64 |
| PubMed ID | 26711255 | Mgi Jnum | J:236207 |
| Mgi Id | MGI:5805357 | Doi | 10.1128/MCB.00930-15 |
| Citation | Ripoche D, et al. (2015) ActivinB Is Induced in Insulinoma To Promote Tumor Plasticity through a beta-Cell-Induced Dedifferentiation. Mol Cell Biol 36(5):756-64 |
| abstractText | Loss of pancreatic beta-cell maturity occurs in diabetes and insulinomas. Although both physiological and pathological stresses are known to promote beta-cell dedifferentiation, little is known about the molecules involved in this process. Here we demonstrate that activinB, a transforming growth factor beta (TGF-beta)-related ligand, is upregulated during tumorigenesis and drives the loss of insulin expression and beta-cell maturity in a mouse insulinoma model. Our data further identify Pax4 as a previously unknown activinB target and potent contributor to the observed beta-cell dedifferentiation. More importantly, using compound mutant mice, we found that deleting activinB expression abolishes tumor beta-cell dedifferentiation and, surprisingly, increases survival without significantly affecting tumor growth. Hence, this work reveals an unexpected role for activinB in the loss of beta-cell maturity, islet plasticity, and progression of insulinoma through its participation in beta-cell dedifferentiation. |
