| RRC ID |
43098
|
| 著者 |
Yoshikawa H, Matsubara K, Zhou X, Okamura S, Kubo T, Murase Y, Shikauchi Y, Esteller M, Herman JG, Wei Wang X, Harris CC.
|
| タイトル |
WNT10B functional dualism: beta-catenin/Tcf-dependent growth promotion or independent suppression with deregulated expression in cancer.
|
| ジャーナル |
Mol Biol Cell
|
| Abstract |
We found aberrant DNA methylation of the WNT10B promoter region in 46% of primary hepatocellular carcinoma (HCC) and 15% of colon cancer samples. Three of 10 HCC and one of two colon cancer cell lines demonstrated low or no expression, and 5-aza-2'deoxycytidine reactivated WNT10B expression with the induction of demethylation, indicating that WNT10B is silenced by DNA methylation in some cancers, whereas WNT10B expression is up-regulated in seven of the 10 HCC cell lines and a colon cancer cell line. These results indicate that WNT10B can be deregulated by either overexpression or silencing in cancer. We found that WNT10B up-regulated beta-catenin/Tcf activity. However, WNT10B-overexpressing cells demonstrated a reduced growth rate and anchorage-independent growth that is independent of the beta-catenin/Tcf activation, because mutant beta-catenin-transduced cells did not suppress growth, and dominant-negative hTcf-4 failed to alleviate the growth suppression by WNT10B. Although WNT10B expression alone inhibits cell growth, it acts synergistically with the fibroblast growth factor (FGF) to stimulate cell growth. WNT10B is bifunctional, one function of which is involved in beta-catenin/Tcf activation, and the other function is related to the down-regulation of cell growth through a different mechanism. We suggest that FGF switches WNT10B from a negative to a positive cell growth regulator.
|
| 巻・号 |
18(11)
|
| ページ |
4292-303
|
| 公開日 |
2007-11-1
|
| DOI |
10.1091/mbc.e06-10-0889
|
| PII |
E06-10-0889
|
| PMID |
17761539
|
| PMC |
PMC2043567
|
| MeSH |
Animals
Cell Line, Tumor
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic*
Mice
Mice, Nude
Neoplasm Metastasis / pathology
Neoplasms / metabolism*
Neoplasms / pathology*
Protein Binding
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism*
RNA, Small Interfering / genetics
TCF Transcription Factors / classification
TCF Transcription Factors / metabolism*
Wnt Proteins / genetics
Wnt Proteins / metabolism*
Xenograft Model Antitumor Assays
beta Catenin / metabolism*
|
| IF |
3.791
|
| 引用数 |
25
|
|
WOS 分野
|
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HuH-7(RCB1366) |
