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Simultaneous activation of impaired autophagy and the mammalian target of rapamycin pathway in oral squamous cell carcinoma
Author(s) -
Yin Xubin,
Hu Liang,
Feng Xiaoyu,
Wang Hongyun,
Zhang Chunmei,
Wang Hao,
Wang Songlin
Publication year - 2019
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12884
Subject(s) - pi3k/akt/mtor pathway , autophagy , rptor , p70 s6 kinase 1 , biology , cancer research , apoptosis , microbiology and biotechnology , signal transduction , biochemistry
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.