Atonal homolog 1 Is a Tumor Suppressor Gene

被引：93

作者：

Bossuyt, Wouter ^{[2
,3
,4
]}

Kazanjian, Avedis ^{[1
]}

De Geest, Natalie ^{[2
,3
]}

Van Kelst, Sofie ^{[2
,3
]}

De Hertogh, Gert ^{[5
]}

Geboes, Karel ^{[5
]}

Boivin, Greg P. ^{[6
]}

Luciani, Judith ^{[7
]}

Fuks, Francois ^{[7
]}

Chuah, Marinee ^{[8
,9
]}

VandenDriessche, Thierry ^{[8
,9
]}

Marynen, Peter ^{[3
,4
,10
]}

Cools, Jan ^{[3
,4
,10
]}

Shroyer, Noah F. ^{[1
,11
,12
]}

Hassan, Bassem A. ^{[2
,3
,4
]}

机构：

[1] Childrens Hosp Res Fdn, Div Gastroenterol Hepatol & Nutr, Cincinnati, OH 45229 USA

[2] VIB, Dept Mol & Dev Genet, Neurogenet Lab, Louvain, Belgium

[3] KU Leuven Sch Med, Dept Human Genet, Louvain, Belgium

[4] KU Leuven Grp Biomed, Doctoral Program Mol & Dev Genet, Louvain, Belgium

[5] Katholieke Univ Leuven, Leuven Univ Hosp, Dept Pathol, Louvain, Belgium

[6] Univ Cincinnati, Coll Med, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA

[7] Free Univ Brussels ULB, Fac Med, Lab Canc Epigenet, Brussels, Belgium

[8] VIB, Vesalius Res Ctr, Louvain, Belgium

[9] KU Leuven Sch Med, Vesalius Res Ctr, Louvain, Belgium

[10] VIB, Dept Mol & Dev Genet, Human Genome Lab, Louvain, Belgium

[11] Childrens Hosp Res Fdn, Div Dev Biol, Cincinnati, OH 45229 USA

[12] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA

来源：

PLOS BIOLOGY | 2009年 / 7卷 / 02期

基金：

美国国家卫生研究院;

关键词：

MERKEL CELL-CARCINOMA; MULTIPLE INTESTINAL NEOPLASIA; NEUROTROPHIN RECEPTORS; NERVOUS-SYSTEM; DROSOPHILA EYE; IN-VIVO; MATH1; CANCER; MOUSE; INHIBITOR;

D O I：

10.1371/journal.pbio.1000039

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：

Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor genes in vivo. Genetic knockouts in mouse and molecular analyses in the mouse and in human cancer cell lines support a tumor suppressor function for ATOH1. ATOH1 antagonizes tumor formation and growth by regulating proliferation and apoptosis, likely via activation of the Jun N-terminal kinase signaling pathway. Furthermore, colorectal cancer and Merkel cell carcinoma patients show genetic and epigenetic ATOH1 loss-of-function mutations. Our data indicate that ATOH1 may be an early target for oncogenic mutations in tissues where it instructs cellular differentiation.

引用

页码：311 / 326

页数：16

共 52 条

[31] K-252A AND STAUROSPORINE SELECTIVELY BLOCK AUTOPHOSPHORYLATION OF NEUROTROPHIN RECEPTORS AND NEUROTROPHIN-MEDIATED RESPONSES [J].

NYE, SH ;

SQUINTO, SP ;

GLASS, DJ ;

STITT, TN ;

HANTZOPOULOS, P ;

MACCHI, MJ ;

LINDSAY, NS ;

IP, NY ;

YANCOPOULOS, GD .

MOLECULAR BIOLOGY OF THE CELL, 1992, 3 (06) :677-686

[32] Colon cancer survival rates with the new American Joint Committee on cancer sixth edition staging [J].

O'Connell, JB ;

Maggard, MA ;

Ko, CY .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2004, 96 (19) :1420-1425

[33] Self-renewal and cancer of the gut: Two sides of a coin [J].

Radtke, F ;

Clevers, H .

SCIENCE, 2005, 307 (5717) :1904-1909

[34]

Ruggeri BA, 1999, CURR MED CHEM, V6, P845

[35] Cell Signaling by Receptor Tyrosine Kinases [J].

Lemmon, Mark A. ;

Schlessinger, Joseph .

CELL, 2010, 141 (07) :1117-1134

[36] Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional γ-secretase inhibitor [J].

Searfoss, GH ;

Jordan, WH ;

Calligaro, DO ;

Galbreath, EJ ;

Schirtzinger, LM ;

Berridge, BR ;

Gao, H ;

Higgins, MA ;

May, PC ;

Ryan, TP .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (46) :46107-46116

[37] L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid β-protein precursor γ-secretase activity [J].

Shearman, MS ;

Beher, D ;

Clarke, EE ;

Lewis, HD ;

Harrison, T ;

Hunt, P ;

Nadin, A ;

Smith, AL ;

Stevenson, G ;

Castro, JL .

BIOCHEMISTRY, 2000, 39 (30) :8698-8704

[38] An inhibitor of c-jun aminoterminal kinase (SP600125) represses c-Jun activation, DNA-binding and PMA-inducible 92-kDa type IV collagenase expression [J].

Shin, M ;

Yan, C ;

Boyd, D .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2002, 1589 (03) :311-316

[39] Intestine-specific ablation of mouse atonal homolog 1 (Math1) reveals a role in cellular homeostasis [J].

Shroyer, Noah F. ;

Helmrath, Michael A. ;

Wang, Vincent Y. -C. ;

Antalffy, Barbara ;

Henning, Susan J. ;

Zoghbi, Huda Y. .

GASTROENTEROLOGY, 2007, 132 (07) :2478-2488

[40] MULTIPLE INTESTINAL NEOPLASIA CAUSED BY A MUTATION IN THE MURINE HOMOLOG OF THE APC GENE [J].

SU, LK ;

KINZLER, KW ;

VOGELSTEIN, B ;

PREISINGER, AC ;

MOSER, AR ;

LUONGO, C ;

GOULD, KA ;

DOVE, WF .

SCIENCE, 1992, 256 (5057) :668-670

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