PMID- 31132188 OWN - NLM STAT- MEDLINE DCOM- 20200109 LR - 20211204 IS - 1600-0714 (Electronic) IS - 0904-2512 (Linking) VI - 48 IP - 8 DP - 2019 Sep TI - Simultaneous activation of impaired autophagy and the mammalian target of rapamycin pathway in oral squamous cell carcinoma. PG - 705-711 LID - 10.1111/jop.12884 [doi] AB - 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. CI - (c) 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Yin, Xubin AU - Yin X AD - Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China. AD - Beijing Tian Tan Hospital, Capital Medical University, Beijing, China. FAU - Hu, Liang AU - Hu L AD - Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China. FAU - Feng, Xiaoyu AU - Feng X AD - Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China. FAU - Wang, Hongyun AU - Wang H AD - Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. FAU - Zhang, Chunmei AU - Zhang C AD - Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China. FAU - Wang, Hao AU - Wang H AD - Beijing Tian Tan Hospital, Capital Medical University, Beijing, China. FAU - Wang, Songlin AU - Wang S AUID- ORCID: 0000-0002-7066-2654 AD - Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China. AD - Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, Beijing, China. LA - eng GR - Beijing Scholar Program-PXM2018_014226_000021/Beijing Municipality Government/ GR - PXM2017_014226_000023/Beijing Municipality Government/ GR - PXM2018_193312_000006_0028S643_FCG/Beijing Municipality Government/ GR - 91649124/National Natural Science Foundation of China/ PT - Journal Article DEP - 20190617 PL - Denmark TA - J Oral Pathol Med JT - Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology JID - 8911934 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Cell Cycle Proteins) RN - 0 (EIF4EBP1 protein, human) RN - 0 (MAP1LC3A protein, human) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Phosphoproteins) RN - 0 (SQSTM1 protein, human) RN - 0 (Sequestosome-1 Protein) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Adaptor Proteins, Signal Transducing/metabolism MH - Aged MH - *Autophagy MH - Carcinoma, Squamous Cell/*metabolism/pathology MH - Cell Cycle Proteins/metabolism MH - Female MH - Humans MH - Male MH - Microtubule-Associated Proteins/metabolism MH - Middle Aged MH - Mouth Neoplasms/*metabolism/pathology MH - Phosphoproteins MH - Phosphorylation MH - Ribosomal Protein S6 Kinases, 70-kDa/metabolism MH - Sequestosome-1 Protein/metabolism MH - *Signal Transduction MH - TOR Serine-Threonine Kinases/*metabolism OTO - NOTNLM OT - autophagy OT - light chain 3 OT - mammalian target of rapamycin OT - oral squamous cell carcinoma OT - p62 EDAT- 2019/05/28 06:00 MHDA- 2020/01/10 06:00 CRDT- 2019/05/28 06:00 PHST- 2019/05/10 00:00 [received] PHST- 2019/05/11 00:00 [accepted] PHST- 2019/05/28 06:00 [pubmed] PHST- 2020/01/10 06:00 [medline] PHST- 2019/05/28 06:00 [entrez] AID - 10.1111/jop.12884 [doi] PST - ppublish SO - J Oral Pathol Med. 2019 Sep;48(8):705-711. doi: 10.1111/jop.12884. Epub 2019 Jun 17.