Details

Autor(en) / Beteiligte

• Lee, I H
• Sohn, M
• Lim, H J
• Yoon, S
• Oh, H
• Shin, S
• Shin, J H
• Oh, S-H
• Kim, J
• Lee, D K
• Noh, D Y
• Bae, D S
• Seong, J K
• Bae, Y S

Titel

Ahnak functions as a tumor suppressor via modulation of TGFβ/Smad signaling pathway

Ist Teil von

• Oncogene, 2014-09, Vol.33 (38), p.4675-4684

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• We provide detailed mechanisms of Ahnak-mediated potentiation of transforming growth factor β (TGFβ) 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 TGFβ-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 TGFβ signaling.