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

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

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
JournalOncogene
Volume33
Issue number38
DOIs
StatePublished - 18 Sep 2014

Fingerprint

Dive into the research topics of 'Ahnak functions as a tumor suppressor via modulation of TGFβ/Smad signaling pathway'. Together they form a unique fingerprint.

Cite this