| RRC ID |
44668
|
| Author |
Inui T, Chano T, Takikita-Suzuki M, Nishikawa M, Yamamoto G, Okabe H.
|
| Title |
Association of p62/SQSTM1 excess and oral carcinogenesis.
|
| Journal |
PLoS One
|
| Abstract |
p62/SQSTM1 (sequestosome1) has never been evaluated in oral epithelium. In order to clarify the role of p62/SQSTM1 in carcinogenesis in oral epithelium, both p62/SQSTM1 and Nrf2 were immunohistochemically evaluated in 54 carcinomas and 14 low grade dysplasias. p62/SQSTM1 knockdowns were also designed in oral cancer cells, and we analyzed the Nrf2 pathway, GSH contents and ROS accumulation. The association between p62/SQSTM1 excess and prognosis was addressed in a clinical cohort of oral carcinoma cases. p62/SQSTM1 excess was more obvious in carcinomas, but Nrf2 was abundant in almost all samples of the oral epithelium. In oral carcinoma cells, p62/SQSTM1 knockdown did not affect the Nrf2-Keap1 pathway but did significantly reduce GSH content with subsequent ROS accumulation, and caused cell growth inhibition in the irradiated condition. Finally, p62/SQSTM1 excess was associated with poor prognosis in a clinical cohort. In oral epithelial carcinogenesis, p62/SQSTM1 excess played a role in GSH induction rather than Nrf2 accumulation, and may cause resistance to cytotoxic stresses such as radiation or chemotherapy. Immunohistochemical evaluation of p62/SQSTM1 may be a potential significant marker to identify early carcinogenesis, chemo-radiotherapeutic resistance or poor prognosis of oral squamous cell carcinomas.
|
| Volume |
8(9)
|
| Pages |
e74398
|
| Published |
2013-1-1
|
| DOI |
10.1371/journal.pone.0074398
|
| PII |
PONE-D-13-09394
|
| PMID |
24086340
|
| PMC |
PMC3782476
|
| MeSH |
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Carcinoma, Squamous Cell / metabolism*
Carcinoma, Squamous Cell / pathology
Cell Line, Tumor
Cohort Studies
Female
Gene Knockdown Techniques
Humans
Male
Middle Aged
Mouth Neoplasms / metabolism*
Mouth Neoplasms / pathology
Prognosis
Sequestosome-1 Protein
|
| IF |
2.74
|
| Times Cited |
26
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
SAS(RCB1974) |
