論文 - 詳細
| RRC ID | 52225 |
|---|---|
| 著者 | Kumazoe M, Takai M, Hiroi S, Takeuchi C, Kadomatsu M, Nojiri T, Onda H, Bae J, Huang Y, Takamatsu K, Yamashita S, Kangawa K, Tachibana H. |
| タイトル | The FOXO3/PGC-1β signaling axis is essential for cancer stem cell properties of pancreatic ductal adenocarcinoma. |
| ジャーナル | J Biol Chem |
| Abstract |
In 95% of patients with pancreatic ductal adenocarcinoma, recurrence is observed following chemotherapy. Findings from several studies have indicated that cancer stem cells (CSCs) are resistant to anticancer agents and may be involved in cancer recurrence and metastasis. The CD44 protein is a major CSC marker, and CD44 also plays an indispensable role in the CSC properties in several cancers, including pancreatic cancer; however, no clinical approach exists to inhibit CD44 activity. Here, we have performed knock-in/knockdown experiments, and we demonstrate that the forkhead box O3 (FOXO3)/liver kinase B1 (LKB1)/AMP-activated protein kinase/peroxisome proliferator-activated receptor-γ co-activator-1β (PGC-1β)/pyruvate dehydrogenase-A1 pathway is essential for CD44 expression and CSC properties. We observed that patients exhibiting high pyruvate dehydrogenase-A1 expression have a poor prognosis. Systemic PGC-1β knock-out mice are fertile and viable and do not exhibit an overt phenotype under normal conditions. This suggests that cGMP induction and PGC-1β inhibition represent potential strategies for treating patients with pancreatic ductal adenocarcinoma. |
| 巻・号 | 292(26) |
| ページ | 10813-10823 |
| 公開日 | 2017-6-30 |
| DOI | 10.1074/jbc.M116.772111 |
| PII | S0021-9258(20)36497-8 |
| PMID | 28507102 |
| PMC | PMC5491768 |
| MeSH | Animals Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Carcinoma, Pancreatic Ductal / genetics Carcinoma, Pancreatic Ductal / metabolism* Carcinoma, Pancreatic Ductal / pathology Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Line, Tumor Female Forkhead Box Protein O3 / genetics Forkhead Box Protein O3 / metabolism* Humans Male Mice, Knockout Neoplasm Proteins / genetics Neoplasm Proteins / metabolism* Neoplastic Stem Cells Pancreatic Neoplasms / genetics Pancreatic Neoplasms / metabolism* Pancreatic Neoplasms / pathology Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism RNA-Binding Proteins Signal Transduction* |
| IF | 4.238 |
| 引用数 | 15 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 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 | PANC-1(RCB2095) |