| First Author | Yoshitomi H | Year | 2021 |
| Journal | Cancer Res | Volume | 81 |
| Issue | 4 | Pages | 945-955 |
| PubMed ID | 33184107 | Mgi Jnum | J:303979 |
| Mgi Id | MGI:6690526 | Doi | 10.1158/0008-5472.CAN-20-1880 |
| Citation | Yoshitomi H, et al. (2021) GSK3beta-Mediated Expression of CUG-Translated WT1 Is Critical for Tumor Progression. Cancer Res 81(4):945-955 |
| abstractText | The Wilms' tumor 1 (WT1) gene is well known as a chameleon gene. It plays a role as a tumor suppressor in Wilms' tumor but also acts as an oncogene in other cancers. Previously, our group reported that a canonical AUG starting site for the WT1 protein (augWT1) acts as a tumor suppressor, whereas a CUG starting site for the WT1 protein (cugWT1) functions as an oncogene. In this study, we report an oncogenic role of cugWT1 in the AOM/DSS-induced colon cancer mouse model and in a urethane-induced lung cancer model in mice lacking cugWT1. Development of chemically-induced tumors was significantly depressed in cugWT1-deficient mice. Moreover, glycogen synthase kinase 3beta promoted phosphorylation of cugWT1 at S64, resulting in ubiquitination and degradation of the cugWT1 associated with the F-box(-/-) WD repeat-containing protein 8. Overall, our findings suggest that inhibition of cugWT1 expression provides a potential candidate target for therapy. SIGNIFICANCE: These findings demonstrate that CUG-translated WT1 plays an oncogenic role in vivo, and GSK3beta-mediated phosphorylation of cugWT1 induces its ubiquitination and degradation in concert with FBXW8. |
