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Simultaneous activation of impaired autophagy and the mammalian target of rapamycin pathway in oral squamous cell carcinoma.
J Oral Pathol Med. 2019 May 27;:
Authors: Yin X, Hu L, Feng X, Wang H, Zhang C, Wang H, Wang S
Abstract
BACKGROUND: The aim of this study was to conduct a comparative evaluation of the expression levels of autophagy markers and proteins of the mammalian target of rapamycin (mTOR) pathway in normal, margin, and tumour tissues of patients with oral squamous cell carcinoma (OSCC).
MATERIALS AND METHODS: Three regional specimens, including normal, margin, and tumour tissues, were collected from 26 patients with OSCC. Western blotting, immunohistochemistry, and immunofluorescence staining were performed to detect mTOR, eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), p70 ribosomal S6 protein kinase (p70S6K), and the corresponding phosphorylated proteins, as well as the light chain 3 (LC3) and sequestosome-1 (SQSTM1, also known as p62) autophagy indicators.
RESULTS: LC3-II, p62, mTOR, phospho-mTOR, 4E-BP1, and phospho-4E-BP1 were highly expressed in the margin and tumour groups. There were positive correlations between mTOR/phospho-mTOR, mTOR/4E-BP1, mTOR/phospho-4E-BP1, mTOR/p70S6K, LC3-II/p62, LC3-II/p70S6K, p62/4E-BP1, and p62/phospho-4E-BP1 in normal group, while LC3-II/p62, LC3-II/mTOR, LC3-II/4E-BP1, LC3-II/phospho-4E-BP1, phospho-4E-BP1/mTOR, phospho-4E-BP1/4E-BP1, and p62/4E-BP1 showed positive relationships in margin group; however, in tumour group, only mTOR/phospho-mTOR, 4E-BP1/phospho-4E-BP1, and phospho-mTOR/p70S6K showed positive correlations.
CONCLUSION: The study suggests that autophagy is impaired in patients with OSCC and impaired autophagy and the mTOR pathway are simultaneously activated in OSCC cells. This article is protected by copyright. All rights reserved.
BACKGROUND: The aim of this study was to conduct a comparative evaluation of the expression levels of autophagy markers and proteins of the mammalian target of rapamycin (mTOR) pathway in normal, margin, and tumour tissues of patients with oral squamous cell carcinoma (OSCC).
MATERIALS AND METHODS: Three regional specimens, including normal, margin, and tumour tissues, were collected from 26 patients with OSCC. Western blotting, immunohistochemistry, and immunofluorescence staining were performed to detect mTOR, eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), p70 ribosomal S6 protein kinase (p70S6K), and the corresponding phosphorylated proteins, as well as the light chain 3 (LC3) and sequestosome-1 (SQSTM1, also known as p62) autophagy indicators.
RESULTS: LC3-II, p62, mTOR, phospho-mTOR, 4E-BP1, and phospho-4E-BP1 were highly expressed in the margin and tumour groups. There were positive correlations between mTOR/phospho-mTOR, mTOR/4E-BP1, mTOR/phospho-4E-BP1, mTOR/p70S6K, LC3-II/p62, LC3-II/p70S6K, p62/4E-BP1, and p62/phospho-4E-BP1 in normal group, while LC3-II/p62, LC3-II/mTOR, LC3-II/4E-BP1, LC3-II/phospho-4E-BP1, phospho-4E-BP1/mTOR, phospho-4E-BP1/4E-BP1, and p62/4E-BP1 showed positive relationships in margin group; however, in tumour group, only mTOR/phospho-mTOR, 4E-BP1/phospho-4E-BP1, and phospho-mTOR/p70S6K showed positive correlations.
CONCLUSION: The study suggests that autophagy is impaired in patients with OSCC and impaired autophagy and the mTOR pathway are simultaneously activated in OSCC cells. This article is protected by copyright. All rights reserved.
PMID: 31132188 [PubMed - as supplied by publisher]
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