| First Author | Tamura T | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 9 | Pages | 2363-2374 |
| PubMed ID | 28209617 | Mgi Jnum | J:242080 |
| Mgi Id | MGI:5904393 | Doi | 10.1158/0008-5472.CAN-16-2114 |
| Citation | Tamura T, et al. (2017) Loss of NDRG2 Expression Confers Oral Squamous Cell Carcinoma with Enhanced Metastatic Potential. Cancer Res 77(9):2363-2374 |
| abstractText | 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-kappaB signaling. Conversely, ectopic expression of NDRG2 reversed the EMT phenotype and inhibited NF-kappaB 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. (c)2017 AACR. |
