RUNX3 attenuates β-catenin/T cell factors in intestinal tumorigenesis

被引：209

作者：

Ito, Kosei ^{[1
,2
]}

Lim, Anthony Chee-Beng ^{[1
]}

Salto-Tellez, Manuel ^{[2
]}

Motoda, Lena ^{[1
]}

Osato, Motomi ^{[1
,2
]}

Shyue, Linda ^{[1
]}

Chuang, Huey ^{[1
]}

Lee, Cecilia Wei Lin ^{[1
]}

Voon, Dominic Chih-Cheng ^{[1
]}

Koo, Jason Kin Wai ^{[2
]}

Wang, Huajing ^{[2
]}

Fukamachi, Hiroshi ^{[3
]}

Ito, Yoshiaki ^{[1
,2
]}

机构：

[1] Inst Mol & Cell Biol, Singapore 138673, Singapore

[2] Natl Univ Singapore, Oncol Res Inst, Yong Loo Lin Sch Med, Singapore 117456, Singapore

[3] Tokyo Med & Dent Univ, Dept Mol Oncol, Bunkyo Ku, Tokyo 1138519, Japan

来源：

CANCER CELL | 2008年 / 14卷 / 03期

关键词：

D O I：

10.1016/j.ccr.2008.08.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In intestinal epithelial cells, inactivation of APC, a key regulator of the Wnt pathway, activates beta-catenin to initiate tumorigenesis. However, other alterations may be involved in intestinal tumorigenesis. Here we found that RUNX3, a gastric tumor suppressor, forms a ternary complex with beta-catenin/7CF4 and attenuates Wnt signaling activity. A significant fraction of human sporadic colorectal adenomas and Runx3(+/-) mouse intestinal adenomas showed inactivation of RUNX3 without apparent beta-catenin accumulation, indicating that RUNX3 inactivation independently induces intestinal adenomas. In human colon cancers, RUNX3 is frequently inactivated with concomitant beta-catenin accumulation, suggesting that adenomas induced by inactivation of RUNX3 may progress to malignancy. Taken together, these data demonstrate that RUNX3 functions as a tumor suppressor by attenuating Wnt signaling.

引用

页码：226 / 237

页数：12

共 40 条

[1] Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine [J].

Andreu, P ;

Colnot, S ;

Godard, C ;

Gad, S ;

Chafey, P ;

Niwa-Kawakita, M ;

Laurent-Puig, P ;

Kahn, A ;

Robine, S ;

Perret, C ;

Romagnolo, B .

DEVELOPMENT, 2005, 132 (06) :1443-1451

[2] β-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/EphrinB [J].

Batlle, E ;

Henderson, JT ;

Beghtel, H ;

van den Born, MMW ;

Sancho, E ;

Huls, G ;

Meeldijk, J ;

Robertson, J ;

van de Wetering, M ;

Pawson, T ;

Clevers, H .

CELL, 2002, 111 (02) :251-263

[3] The RUNX genes: Gain or loss of function in cancer [J].

Blyth, K ;

Cameron, ER ;

Neil, JC .

NATURE REVIEWS CANCER, 2005, 5 (05) :376-387

[4] Cancer genetics: colorectal cancer as a model [J].

Bodmer, WF .

JOURNAL OF HUMAN GENETICS, 2006, 51 (05) :391-396

[5] Loss of Runx3 function in leukocytes is associated with spontaneously developed colitis and gastric mucosal hyperplasia [J].

Brenner, O ;

Levanon, D ;

Negreanu, V ;

Golubkov, O ;

Fainaru, O ;

Woolf, E ;

Groner, Y .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (45) :16016-16021

[6] RUNX3 suppresses gastric epithelial cell growth by inducing p21WAF1/Cip1 expression in cooperation with transforming growth factor β-activated SMAD [J].

Chi, XZ ;

Yang, JO ;

Lee, KY ;

Ito, K ;

Sakakura, C ;

Li, QL ;

Kim, HR ;

Cha, EJ ;

Lee, YH ;

Kaneda, A ;

Ushijima, T ;

Kim, WJ ;

Ito, Y ;

Bae, SC .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (18) :8097-8107

[7] TGF-β signaling in tumor suppression and cancer progression [J].

Derynck, R ;

Akhurst, RJ ;

Balmain, A .

NATURE GENETICS, 2001, 29 (02) :117-129

[8] Epigenetic inactivation of RUNX3 in microsatellite unstable sporadic colon cancers [J].

Goel, A ;

Arnold, CN ;

Tassone, P ;

Chang, DK ;

Niedzwiecki, D ;

Dowell, JM ;

Wasserman, L ;

Compton, C ;

Mayer, RJ ;

Bertagnolli, MM ;

Boland, CR .

INTERNATIONAL JOURNAL OF CANCER, 2004, 112 (05) :754-759

[9] The CpG island methylator phenotype and chromosomal instability are inversely correlated in sporadic colorectal cancer [J].

Goel, Ajay ;

Nagasaka, Takeshi ;

Arnold, Christian N. ;

Inoue, Toru ;

Hamilton, Cody ;

Niedzwiecki, Donna ;

Compton, Carolyn ;

Mayer, Robert J. ;

Goldberg, Richard ;

Bertagnolli, Monica M. ;

Boland, C. Richard .

GASTROENTEROLOGY, 2007, 132 (01) :127-138

[10] Inhibition of growth of mouse gastric cancer cells by Runx3, a novel tumor suppressor [J].

Guo, WH ;

Weng, LQ ;

Ito, K ;

Chen, LF ;

Nakanishi, H ;

Tatematsu, M ;

Ito, Y .

ONCOGENE, 2002, 21 (54) :8351-8355

← 1 2 3 4 →