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

被引：107

作者：

Lee, I. H. ^{[1
,2
]}

Sohn, M. ^{[1
,2
]}

Lim, H. J. ^{[1
,2
]}

Yoon, S. ^{[1
,2
]}

Oh, H. ^{[1
,2
]}

Shin, S. ^{[1
,2
]}

Shin, J. H. ^{[3
]}

Oh, S-H ^{[4
]}

Kim, J. ^{[1
,2
]}

Lee, D. K. ^{[1
,2
]}

Noh, D. Y. ^{[5
]}

Bae, D. S. ^{[6
]}

Seong, J. K. ^{[3
]}

Bae, Y. S. ^{[1
,2
]}

机构：

[1] Ewha Womans Univ, Dept Life Sci, Seoul, South Korea

[2] Ewha Womans Univ, GT5 program, Seoul, South Korea

[3] Seoul Natl Univ, Coll Vet Med, Lab Dev Biol & Genom, Seoul 151742, South Korea

[4] Gachon Univ, Coll Pharm, Inchon, South Korea

[5] Seoul Natl Univ, Sch Med, Dept Surg, Seoul 151742, South Korea

[6] Sungkyunkwan Univ, Samsung Hosp, Dept Obstet & Gynecol, Seoul, South Korea

来源：

ONCOGENE | 2014年 / 33卷 / 38期

基金：

新加坡国家研究基金会;

关键词：

MAMMARY-GLAND DEVELOPMENT; C-MYC; BETA; PROTEIN; IDENTIFICATION; TARGET; GENE; PHOSPHATASE; COMPLEX;

D O I：

10.1038/onc.2014.69

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：4675 / 4684

页数：10

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