| RRC ID |
62782
|
| Author |
Tamura T, Ichikawa T, Nakahata S, Kondo Y, Tagawa Y, Yamamoto K, Nagai K, Baba T, Yamaguchi R, Futakuchi M, Yamashita Y, Morishita K.
|
| Title |
Loss of NDRG2 Expression Confers Oral Squamous Cell Carcinoma with Enhanced Metastatic Potential.
|
| Journal |
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.
|
| Volume |
77(9)
|
| Pages |
2363-2374
|
| Published |
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
|
| Resource |
| Human and Animal Cells |
Ca9-22(RCB1976)
HSC-2(RCB1945)
HSC-4(RCB1902)
Sa3(RCB0980)
HSQ-89(RCB0789)
SAS(RCB1974)
HO-1-u-1(RCB2102) |
