Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling

Masahiro Sonoshita; Masahiro Aoki; Haruhiko Fuwa; Koji Aoki; Hisahiro Hosogi; Yoshiharu Sakai; Hiroki Hashida; Arimichi Takabayashi; Makoto Sasaki; Sylvie Robine; Kazuyuki Itoh; Kiyoko Yoshioka; Fumihiko Kakizaki; Takanori Kitamura; Masanobu Oshima; Makoto Mark Taketo

doi:10.1016/j.ccr.2010.11.008

Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling

Masahiro Sonoshita, Masahiro Aoki, Haruhiko Fuwa, Koji Aoki, Hisahiro Hosogi, Yoshiharu Sakai, Hiroki Hashida, Arimichi Takabayashi, Makoto Sasaki, Sylvie Robine, Kazuyuki Itoh, Kiyoko Yoshioka, Fumihiko Kakizaki, Takanori Kitamura, Masanobu Oshima, Makoto Mark Taketo

School of Regeneration and Repair

Research output: Contribution to journal › Article › peer-review

Abstract

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(Δ716) 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.

Original language	English
Pages (from-to)	125-37
Number of pages	13
Journal	Cancer Cell
Volume	19
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2010.11.008
Publication status	Published - 18 Jan 2011

Keywords / Materials (for Non-textual outputs)

Animals
Benzodiazepinones
Cell Line, Tumor
Colonic Neoplasms
Down-Regulation
Gene Expression
Gene Silencing
HCT116 Cells
Humans
Immunoglobulin J Recombination Signal Sequence-Binding Protein
Intestinal Polyposis
Ligands
Liver Neoplasms
Lung Neoplasms
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Mutant Strains
Mice, Nude
Mice, Transgenic
Models, Biological
Neoplasm Invasiveness
Neoplasm Metastasis
Nuclear Matrix
Receptor, Notch1
Receptors, Notch
Repressor Proteins
Signal Transduction
Stromal Cells
Transcription Factors
Transendothelial and Transepithelial Migration

Access to Document

10.1016/j.ccr.2010.11.008

Cite this

@article{861606e3db0c431f9aeeef440d540205,

title = "Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling",

abstract = "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(Δ716) 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.",

keywords = "Animals, Benzodiazepinones, Cell Line, Tumor, Colonic Neoplasms, Down-Regulation, Gene Expression, Gene Silencing, HCT116 Cells, Humans, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Intestinal Polyposis, Ligands, Liver Neoplasms, Lung Neoplasms, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, Nude, Mice, Transgenic, Models, Biological, Neoplasm Invasiveness, Neoplasm Metastasis, Nuclear Matrix, Receptor, Notch1, Receptors, Notch, Repressor Proteins, Signal Transduction, Stromal Cells, Transcription Factors, Transendothelial and Transepithelial Migration",

author = "Masahiro Sonoshita and Masahiro Aoki and Haruhiko Fuwa and Koji Aoki and Hisahiro Hosogi and Yoshiharu Sakai and Hiroki Hashida and Arimichi Takabayashi and Makoto Sasaki and Sylvie Robine and Kazuyuki Itoh and Kiyoko Yoshioka and Fumihiko Kakizaki and Takanori Kitamura and Masanobu Oshima and Taketo, \{Makoto Mark\}",

year = "2011",

month = jan,

day = "18",

doi = "10.1016/j.ccr.2010.11.008",

language = "English",

volume = "19",

pages = "125--37",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "1",

}

TY - JOUR

T1 - Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling

AU - Sonoshita, Masahiro

AU - Aoki, Masahiro

AU - Fuwa, Haruhiko

AU - Aoki, Koji

AU - Hosogi, Hisahiro

AU - Sakai, Yoshiharu

AU - Hashida, Hiroki

AU - Takabayashi, Arimichi

AU - Sasaki, Makoto

AU - Robine, Sylvie

AU - Itoh, Kazuyuki

AU - Yoshioka, Kiyoko

AU - Kakizaki, Fumihiko

AU - Kitamura, Takanori

AU - Oshima, Masanobu

AU - Taketo, Makoto Mark

PY - 2011/1/18

Y1 - 2011/1/18

N2 - 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(Δ716) 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.

AB - 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(Δ716) 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.

KW - Animals

KW - Benzodiazepinones

KW - Cell Line, Tumor

KW - Colonic Neoplasms

KW - Down-Regulation

KW - Gene Expression

KW - Gene Silencing

KW - HCT116 Cells

KW - Humans

KW - Immunoglobulin J Recombination Signal Sequence-Binding Protein

KW - Intestinal Polyposis

KW - Ligands

KW - Liver Neoplasms

KW - Lung Neoplasms

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Mice, Mutant Strains

KW - Mice, Nude

KW - Mice, Transgenic

KW - Models, Biological

KW - Neoplasm Invasiveness

KW - Neoplasm Metastasis

KW - Nuclear Matrix

KW - Receptor, Notch1

KW - Receptors, Notch

KW - Repressor Proteins

KW - Signal Transduction

KW - Stromal Cells

KW - Transcription Factors

KW - Transendothelial and Transepithelial Migration

U2 - 10.1016/j.ccr.2010.11.008

DO - 10.1016/j.ccr.2010.11.008

M3 - Article

C2 - 21251616

SN - 1535-6108

VL - 19

SP - 125

EP - 137

JO - Cancer Cell

JF - Cancer Cell

IS - 1

ER -

Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling

Abstract

Keywords / Materials (for Non-textual outputs)

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