論文 - 詳細
| RRC ID | 37631 |
|---|---|
| 著者 | Saito RA, Watabe T, Horiguchi K, Kohyama T, Saitoh M, Nagase T, Miyazono K. |
| タイトル | Thyroid transcription factor-1 inhibits transforming growth factor-beta-mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells. |
| ジャーナル | Cancer Res |
| Abstract |
Thyroid transcription factor-1 (TTF-1) is expressed in lung cancer, but its functional roles remain unexplored. TTF-1 gene amplification has been discovered in a part of lung adenocarcinomas, and its action as a lineage-specific oncogene is highlighted. Epithelial-to-mesenchymal transition (EMT) is a crucial event for cancer cells to acquire invasive and metastatic phenotypes and can be elicited by transforming growth factor-beta (TGF-beta). Mesenchymal-to-epithelial transition (MET) is the inverse process of EMT; however, signals that induce MET are largely unknown. Here, we report a novel functional aspect of TTF-1 that inhibits TGF-beta-mediated EMT and restores epithelial phenotype in lung adenocarcinoma cells. This effect was accompanied by down-regulation of TGF-beta target genes, including presumed regulators of EMT, such as Snail and Slug. Moreover, silencing of TTF-1 enhanced TGF-beta-mediated EMT. Thus, TTF-1 can exert a tumor-suppressive effect with abrogation of cellular response to TGF-beta and attenuated invasive capacity. We further revealed that TTF-1 down-regulates TGF-beta2 production in A549 cells and that TGF-beta conversely decreases endogenous TTF-1 expression, suggesting that enhancement of autocrine TGF-beta signaling accelerates the decrease of TTF-1 expression and vice versa. These findings delineate potential links between TTF-1 and TGF-beta signaling in lung cancer progression through regulation of EMT and MET and suggest that modulation of TTF-1 expression can be a novel therapeutic strategy for treatment of lung adenocarcinoma. |
| 巻・号 | 69(7) |
| ページ | 2783-91 |
| 公開日 | 2009-4-1 |
| DOI | 10.1158/0008-5472.CAN-08-3490 |
| PII | 0008-5472.CAN-08-3490 |
| PMID | 19293183 |
| MeSH | Adenocarcinoma / genetics Adenocarcinoma / metabolism* Adenocarcinoma / pathology Animals Cadherins / biosynthesis Cadherins / genetics Carcinoma, Lewis Lung / genetics Carcinoma, Lewis Lung / metabolism Carcinoma, Lewis Lung / pathology Cell Line, Tumor Cell Movement / physiology Cloning, Molecular DNA-Binding Proteins / biosynthesis* DNA-Binding Proteins / deficiency DNA-Binding Proteins / genetics Epithelial Cells / pathology Humans Lung Neoplasms / genetics Lung Neoplasms / metabolism* Lung Neoplasms / pathology Matrix Metalloproteinase 2 / metabolism Mesoderm / pathology Mice Mice, Inbred C57BL Neoplasm Invasiveness Signal Transduction Transcription Factors Transforming Growth Factor beta / antagonists & inhibitors* Transforming Growth Factor beta / metabolism Transforming Growth Factor beta / pharmacology |
| IF | 9.727 |
| 引用数 | 93 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | LC-2/ad(RCB0440) |