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

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

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95 Scopus citations


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.

Original languageEnglish
Pages (from-to)4675-4684
Number of pages10
Issue number38
StatePublished - 18 Sep 2014

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant (No. 2012R1A5A1048236), by the Drug Target Validation program (No. 2009-0093987), by the Bio & Medical Technology Development Program (No. 2012M3A9B4028785) and by Redoxomics grant (No. 2012M3A9C5048708) funded by Ministry of Science, ICT & Future Planning, and the Ewha Womans University Research Grant of 2013 (to I.H.L.).

Publisher Copyright:
© 2014 Macmillan Publishers Limited All rights reserved.


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