論文 - 詳細
| RRC ID | 62782 |
|---|---|
| 著者 | Tamura T, Ichikawa T, Nakahata S, Kondo Y, Tagawa Y, Yamamoto K, Nagai K, Baba T, Yamaguchi R, Futakuchi M, Yamashita Y, Morishita K. |
| タイトル | Loss of NDRG2 Expression Confers Oral Squamous Cell Carcinoma with Enhanced Metastatic Potential. |
| ジャーナル | Cancer Res |
| Abstract |
Loss of the tumor suppressor NDRG2 has been implicated in the development of oral squamous cell carcinoma (OSCC), acting by modulating PI3K/AKT-mediated dephosphorylation of PTEN at S380/S382/T383 (STT). Here, we show that the majority of OSCC tumors with lymph node metastasis, a major prognostic factor, exhibit high levels of phosphorylated AKT-S473 and PTEN-STT and low levels of NDRG2 expression. In Ndrg2-deficient mice, which develop a wide range of tumors, we developed a model of OSCC by treatment with the tobacco surrogate 4-nitroquinoline-1-oxide (4-NQO). In this model, both the number and size of OSCC tumors were increased significantly by Ndrg2 deficiency, which also increased invasion of cervical lymph nodes. 4-NQO treatment of human OSCC cell lines exhibiting low NDRG2 expression induced epithelial-mesenchymal transition via activation of NF-κB signaling. Conversely, ectopic expression of NDRG2 reversed the EMT phenotype and inhibited NF-κB signaling via suppression of PTEN-STT and AKT-S473 phosphorylation. Our results show how NDRG2 expression serves as a critical determinant of the invasive and metastatic capacity of OSCC. Cancer Res; 77(9); 2363-74. ©2017 AACR. |
| 巻・号 | 77(9) |
| ページ | 2363-2374 |
| 公開日 | 2017-5-1 |
| DOI | 10.1158/0008-5472.CAN-16-2114 |
| PII | 0008-5472.CAN-16-2114 |
| PMID | 28209617 |
| MeSH | 4-Nitroquinoline-1-oxide / toxicity Adaptor Proteins, Signal Transducing Animals Carcinoma, Squamous Cell / chemically induced Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / pathology Cell Line, Tumor Disease Models, Animal Epithelial-Mesenchymal Transition / drug effects Gene Expression Regulation, Neoplastic Humans Lymphatic Metastasis / genetics* Lymphatic Metastasis / pathology Mice Mouth Neoplasms / chemically induced Mouth Neoplasms / genetics* Mouth Neoplasms / pathology NF-kappa B / genetics Oncogene Protein v-akt / genetics PTEN Phosphohydrolase / genetics Phosphatidylinositol 3-Kinases / genetics Phosphorylation Proteins / genetics* Signal Transduction / drug effects |
| IF | 9.727 |
| 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 | 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 | Ca9-22(RCB1976) HSC-2(RCB1945) HSC-4(RCB1902) Sa3(RCB0980) HSQ-89(RCB0789) SAS(RCB1974) HO-1-u-1(RCB2102) |