| First Author | Pignatti E | Year | 2020 |
| Journal | Cell Rep | Volume | 31 |
| Issue | 3 | Pages | 107524 |
| PubMed ID | 32320669 | Mgi Jnum | J:303487 |
| Mgi Id | MGI:6514540 | Doi | 10.1016/j.celrep.2020.107524 |
| Citation | Pignatti E, et al. (2020) Beta-Catenin Causes Adrenal Hyperplasia by Blocking Zonal Transdifferentiation. Cell Rep 31(3):107524 |
| abstractText | Activating mutations in the canonical Wnt/beta-catenin pathway are key drivers of hyperplasia, the gateway for tumor development. In a wide range of tissues, this occurs primarily through enhanced effects on cellular proliferation. Whether additional mechanisms contribute to beta-catenin-driven hyperplasia remains unknown. The adrenal cortex is an ideal system in which to explore this question, as it undergoes hyperplasia following somatic beta-catenin gain-of-function (betacat-GOF) mutations. Targeting betacat-GOF to zona Glomerulosa (zG) cells leads to a progressive hyperplastic expansion in the absence of increased proliferation. Instead, we find that hyperplasia results from a functional block in the ability of zG cells to transdifferentiate into zona Fasciculata (zF) cells. Mechanistically, zG cells demonstrate an upregulation of Pde2a, an inhibitor of zF-specific cAMP/PKA signaling. Hyperplasia is further exacerbated by trophic factor stimulation leading to organomegaly. Together, these data indicate that beta-catenin drives adrenal hyperplasia through both proliferation-dependent and -independent mechanisms. |
