Association of p62/SQSTM1 excess and oral carcinogenesis.
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 designe...
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doaj-d1f1a7b19989432fa1f19ce7ee4288782020-11-24T22:00:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7439810.1371/journal.pone.0074398Association of p62/SQSTM1 excess and oral carcinogenesis.Takuma InuiTokuhiro ChanoMikiko Takikita-SuzukiMasanori NishikawaGaku YamamotoHidetoshi Okabep62/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.http://europepmc.org/articles/PMC3782476?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Takuma Inui Tokuhiro Chano Mikiko Takikita-Suzuki Masanori Nishikawa Gaku Yamamoto Hidetoshi Okabe |
spellingShingle |
Takuma Inui Tokuhiro Chano Mikiko Takikita-Suzuki Masanori Nishikawa Gaku Yamamoto Hidetoshi Okabe Association of p62/SQSTM1 excess and oral carcinogenesis. PLoS ONE |
author_facet |
Takuma Inui Tokuhiro Chano Mikiko Takikita-Suzuki Masanori Nishikawa Gaku Yamamoto Hidetoshi Okabe |
author_sort |
Takuma Inui |
title |
Association of p62/SQSTM1 excess and oral carcinogenesis. |
title_short |
Association of p62/SQSTM1 excess and oral carcinogenesis. |
title_full |
Association of p62/SQSTM1 excess and oral carcinogenesis. |
title_fullStr |
Association of p62/SQSTM1 excess and oral carcinogenesis. |
title_full_unstemmed |
Association of p62/SQSTM1 excess and oral carcinogenesis. |
title_sort |
association of p62/sqstm1 excess and oral carcinogenesis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3782476?pdf=render |
work_keys_str_mv |
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