| RRC ID |
28430
|
| 著者 |
Chevillard-Briet M, Quaranta M, Grézy A, Mattera L, Courilleau C, Philippe M, Mercier P, Corpet D, Lough J, Ueda T, Fukunaga R, Trouche D, Escaffit F.
|
| タイトル |
Interplay between chromatin-modifying enzymes controls colon cancer progression through Wnt signaling.
|
| ジャーナル |
Hum Mol Genet
|
| Abstract |
Cancer progression is associated with epigenetic alterations, such as changes in DNA methylation, histone modifications or variants incorporation. The p400 ATPase, which can incorporate the H2A.Z variant, and the Tip60 histone acetyltransferase are interacting chromatin-modifying proteins crucial for the control of cell proliferation. We demonstrate here that Tip60 acts as a tumor suppressor in colon, since mice heterozygous for Tip60 are more susceptible to chemically induced preneoplastic lesions and adenomas. Strikingly, heterozygosity for p400 reverses the Tip60-dependent formation of preneoplastic lesions, uncovering for the first time pro-oncogenic functions for p400. By genome-wide analysis and using a specific inhibitor in vivo, we demonstrated that these effects are dependent on Wnt signaling which is antagonistically impacted by p400 and Tip60: p400 directly favors the expression of a subset of Wnt-target genes and regulators, whereas Tip60 prevents β-catenin acetylation and activation. Taken together, our data underline the physiopathological importance of interplays between chromatin-modifying enzymes in the control of cancer-related signaling pathways.
|
| 巻・号 |
23(8)
|
| ページ |
2120-31
|
| 公開日 |
2014-4-15
|
| DOI |
10.1093/hmg/ddt604
|
| PII |
ddt604
|
| PMID |
24287617
|
| MeSH |
Acetylation
Animals
Blotting, Western
Cells, Cultured
Chromatin / metabolism
Chromatin Immunoprecipitation
Colonic Neoplasms / genetics
Colonic Neoplasms / metabolism*
Colonic Neoplasms / pathology*
Disease Progression
Female
Gene Expression Profiling
Histone Acetyltransferases / metabolism
Histone Acetyltransferases / physiology*
Histones / metabolism*
Inositol 1,4,5-Trisphosphate Receptors / physiology*
Lysine Acetyltransferase 5
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Precancerous Conditions / genetics
Precancerous Conditions / metabolism
Precancerous Conditions / pathology
Protein Processing, Post-Translational
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Trans-Activators / physiology*
Wnt Proteins / genetics
Wnt Proteins / metabolism*
beta Catenin / metabolism
|
| IF |
5.101
|
| 引用数 |
17
|
|
WOS 分野
|
GENETICS & HEREDITY
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC01774 |
