| First Author | Lee IH | Year | 2014 |
| Journal | Oncogene | Volume | 33 |
| Issue | 38 | Pages | 4675-84 |
| PubMed ID | 24662814 | Mgi Jnum | J:214424 |
| Mgi Id | MGI:5602941 | Doi | 10.1038/onc.2014.69 |
| Citation | Lee IH, et al. (2014) Ahnak functions as a tumor suppressor via modulation of TGFbeta/Smad signaling pathway. Oncogene 33(38):4675-84 |
| abstractText | We provide detailed mechanisms of Ahnak-mediated potentiation of transforming growth factor beta (TGFbeta) signaling, which leads to a negative regulation of cell growth. We show that Smad3 interacts with Ahnak through MH2 domain and that Ahnak stimulates Smad3 localization into nucleus leading to potentiating TGFbeta-induced transcriptional activity of R-Smad. Moreover, overexpression of Ahnak resulted in growth retardation and cell cycle arrest through downregulation of c-Myc and cyclin D1/D2. We describe results from analyses of Ahnak(-/-) mouse model expressing middle T antigen in a mammary gland-specific manner (MMTV(Tg/+)Ahnak(-/-)), which showed significantly progressed hyperplasia of mammary glands compared with MMTV(Tg/+)Ahnak(+/+). Finally, we screened multiple human breast cancer tissues and showed that the expression of Ahnak in cancer tissues is lower than that in control tissues by 50%. Taken together, these data indicate that Ahnak mediates a negative regulation of cell growth and acts as novel tumor suppressor through potentiation of TGFbeta signaling. |
