Association of p62/SQSTM1 excess and oral carcinogenesis.
Association of p62/SQSTM1 excess and oral carcinogenesis.
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DOI：
10.1371/journal.pone.0074398
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Okabe H
中科院分区：
文献类型：
--
作者：
Inui T;Chano T;Takikita-Suzuki M;Nishikawa M;Yamamoto G;Okabe H
p62/SQSTM1（自噬相关蛋白1）从未在口腔上皮中进行过评估。为了阐明p62/SQSTM1在口腔上皮癌变中的作用，对54例癌组织和14例低级别上皮内瘤变进行了p62/SQSTM1和Nrf2的免疫组化评估。还在口腔癌细胞中设计了p62/SQSTM1基因敲低实验，并分析了Nrf2通路、谷胱甘肽（GSH）含量和活性氧（ROS）积累。在一个口腔癌临床队列中探讨了p62/SQSTM1过量与预后的关系。p62/SQSTM1过量在癌组织中更为明显，但Nrf2在几乎所有口腔上皮样本中都很丰富。在口腔癌细胞中，p62/SQSTM1基因敲低不影响Nrf2 - Keap1通路，但显著降低了GSH含量，随后导致ROS积累，并在照射条件下抑制细胞生长。最后，在一个临床队列中，p62/SQSTM1过量与不良预后相关。在口腔上皮癌变过程中，p62/SQSTM1过量在诱导GSH方面起作用，而非在Nrf2积累方面，并且可能导致对细胞毒性应激（如放疗或化疗）产生抗性。p62/SQSTM1的免疫组化评估可能是识别口腔鳞状细胞癌早期癌变、放化疗抗性或不良预后的一个潜在重要标志物。
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.
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影响因子：
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作者：
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影响因子：
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DOI：
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DOI：
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发表时间：
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影响因子：
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作者：
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