Simultaneous activation of impaired autophagy and the mammalian target of rapamycin pathway in oral squamous cell carcinoma.

Abstract

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). 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. 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. The study suggests that autophagy is impaired in patients with OSCC and impaired autophagy and the mTOR pathway are simultaneously activated in OSCC cells.