Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling

被引：188

作者：

Sonoshita, Masahiro ^{[1
]}

Aoki, Masahiro ^{[1
,7
]}

Fuwa, Haruhiko ^{[2
]}

Aoki, Koji ^{[1
]}

Hosogi, Hisahiro ^{[1
,3
]}

Sakai, Yoshiharu ^{[3
]}

Hashida, Hiroki ^{[4
]}

Takabayashi, Arimichi ^{[4
]}

Sasaki, Makoto ^{[2
]}

Robine, Sylvie ^{[5
]}

Itoh, Kazuyuki ^{[6
]}

Yoshioka, Kiyoko ^{[6
]}

Kakizaki, Fumihiko ^{[1
]}

Kitamura, Takanori ^{[1
]}

Oshima, Masanobu ^{[1
]}

Taketo, Makoto Mark ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto 6068501, Japan

[2] Tohoku Univ, Grad Sch Life Sci, Lab Biostruct Chem, Sendai, Miyagi 9818555, Japan

[3] Kyoto Univ, Grad Sch Med, Dept Surg, Kyoto 6068501, Japan

[4] Kitano Hosp, Dept Gastroenterol Surg & Oncol, Osaka 5308480, Japan

[5] Inst Curie, Equipe Morphogenese & Signalisat Cellulaires, F-75248 Paris, France

[6] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Biol, Osaka 5378511, Japan

[7] Aichi Canc Ctr, Res Inst, Div Mol Pathol, Nagoya, Aichi 4648681, Japan

来源：

CANCER CELL | 2011年 / 19卷 / 01期

关键词：

MOUSE MODELS; MICE; GENE; TUMORIGENESIS; REPRESSION; INDUCTION; RECEPTOR; PATHWAY; DISEASE; COMPLEX;

D O I：

10.1016/j.ccr.2010.11.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Metastasis is responsible for most cancer deaths. Here, we show that Aes (or Grg5) gene functions as an endogenous metastasis suppressor. Expression of Aes was decreased in liver metastases compared with primary colon tumors in both mice and humans. Aes inhibited Notch signaling by converting active Rbpj transcription complexes into repression complexes on insoluble nuclear matrix. In tumor cells, Notch signaling was triggered by ligands on adjoining blood vessels, and stimulated transendothelial migration. Genetic depletion of Aes in Apc(Delta 716) intestinal polyposis mice caused marked tumor invasion and intravasation that were suppressed by Notch signaling inhibition. These results suggest that inhibition of Notch signaling can be a promising strategy for prevention and treatment of colon cancer metastasis.

引用

页码：125 / 137

页数：13

共 46 条

[1] Notch signaling: Cell fate control and signal integration in development [J].

Artavanis-Tsakonas, S ;

Rand, MD ;

Lake, RJ .

SCIENCE, 1999, 284 (5415) :770-776

[2] All Tcf HMG box transcription factors interact with Groucho-related co-repressors [J].

Brantjes, H ;

Roose, J ;

van de Wetering, M ;

Clevers, H .

NUCLEIC ACIDS RESEARCH, 2001, 29 (07) :1410-1419

[3] TCF and Groucho-related genes influence pituitary growth and development [J].

Brinkmeier, ML ;

Potok, MA ;

Cha, KB ;

Gridley, T ;

Stifani, S ;

Meeldijk, J ;

Clevers, H ;

Camper, SA .

MOLECULAR ENDOCRINOLOGY, 2003, 17 (11) :2152-2161

[4] New signals from the invasive front [J].

Christofori, G .

NATURE, 2006, 441 (7092) :444-450

[5]

CORBETT TH, 1975, CANCER RES, V35, P2434

[6] A QUICKSCORE METHOD FOR IMMUNOHISTOCHEMICAL SEMIQUANTITATION - VALIDATION FOR ESTROGEN-RECEPTOR IN BREAST CARCINOMAS [J].

DETRE, S ;

JOTTI, GS ;

DOWSETT, M .

JOURNAL OF CLINICAL PATHOLOGY, 1995, 48 (09) :876-878

[7] Identification of a nuclear domain with deacetylase activity [J].

Downes, M ;

Ordentlich, P ;

Kao, HY ;

Alvarez, JGA ;

Evans, RM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (19) :10330-10335

[8] Tissue-specific and inducible Cre-mediated recombination in the gut epithelium [J].

El Marjou, F ;

Janssen, KP ;

Chang, BHJ ;

Li, M ;

Hindie, V ;

Chan, L ;

Louvard, D ;

Chambon, P ;

Metzger, D ;

Robine, S .

GENESIS, 2004, 39 (03) :186-193

[9] Timeline - The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited [J].

Fidler, IJ .

NATURE REVIEWS CANCER, 2003, 3 (06) :453-458

[10] Mammalian Groucho homologs: Redundancy or specificity? [J].

Gasperowicz, M ;

Otto, F .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2005, 95 (04) :670-687

← 1 2 3 4 5 →