Ahnak functions as a tumor suppressor via modulation of TGF beta/Smad signaling pathway
- 등재 SCIE, SCOPUS
- 발행기관 NATURE PUBLISHING GROUP
- 발행년도 2014
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000108855
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/onc.2014.69
초록/요약
We provide detailed mechanisms of Ahnak-mediated potentiation of transforming growth factor beta (TGF beta) 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 TGF beta-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 (MMTVTg/+ Ahnak(-/-)), which showed significantly progressed hyperplasia of mammary glands compared with MMTVTg/+ 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 TGF beta signaling.
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