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

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.

FOXD1-mTOR Signaling Pathway on Oral Squamous Cell Carcinoma and Its Inhibition by Rosemary Extract (Invitro-Study)

“…mTOR, which is an autophagy molecule, seems to be a highly promising marker to handle patients with solid malignancies, based on applying targeted therapeutic strategies (Mastronikolis et al, 2017). Our mTOR results agreed with Yin et al, (2019). They stated that the overexpression of mTOR protein in OSCC was clarified as a coincidence of upstream oncogene overactivation combined with suppressor gene downregulation, whereas its pure mutations are very rare.…”

p-S6 as a Prognostic Biomarker in Canine Oral Squamous Cell Carcinoma

“…Increasing attention has been paid to the mTOR pathway specially because it could be a potential target for cancer therapy in both dogs and humans [ 15 , 16 , 21 , 23 , 26 , 27 , 41 , 42 , 43 , 44 , 45 , 46 ]. This is directed to decrease the activity of tumour cell using single molecules such as everolimus, curcumin or in combination with other therapies [ 47 , 48 , 49 ], to decrease the resistance to chemotherapy by mTOR inhibition (e.g., temsirolimus) [ 50 ] and radiotherapy [ 51 ] and interestingly also to prevent oral cancer, by its use in human oral potentially malignant disorders (OPMD), where the use of molecules such as metformin, or other molecules decreased these premalignant lesions with decreased mTOR activity [ 24 ].…”

Autophagy Regulation by the Translation Machinery and Its Implications in Cancer

“…Also in yeast, the RNA-binding protein Psp2 is a positive translational regulator of autophagy. Under nitrogenstarvation, Psp2 binds the eIF4E/eIF4G complex and the 5 ′ -UTR of ATG1 and ATG13 mRNAs to promote their translation (70).…”