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Int. J. Mol. Sci. 2017, 18(9), 1920;

Monitoring Autophagy Immunohistochemically and Ultrastructurally during Human Head and Neck Carcinogenesis. Relationship with the DNA Damage Response Pathway

Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece
Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research “Demokritos”, 15310 Athens, Greece
Department of Otolaryngology, Head and Neck Surgery, “Hippokration” General Hospital, National and Kapodistrian University of Athens, 114 Queen Sofia Avenue, 11527 Athens, Greece
Department of Pathology, Democritus University of Thrace, School of Medicine, 68100 Alexandroupolis, Greece
Faculty Institute for Cancer Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester MP13 9PL, UK
Biomedical Research Foundation of the Academy of Athens, 4 Soranou Ephessiou Street, 11527 Athens, Greece
This work is dedicated to the memory of Petros Karakitsos.
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Received: 11 August 2017 / Revised: 1 September 2017 / Accepted: 3 September 2017 / Published: 7 September 2017
(This article belongs to the Special Issue Mechanisms Leading to Genomic Instability)
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Autophagy is a catabolic process that preserves cellular homeostasis. Its exact role during carcinogenesis is not completely defined. Specifically in head and neck cancer, such information from clinical settings that comprise the whole spectrum of human carcinogenesis is very limited. Towards this direction, we examined the in situ status of the autophagy-related factors, Beclin-1, microtubule-associated protein 1 light chain 3, member B (LC3B) and sequestosome 1/p62 (p62) in clinical material covering all histopathological stages of human head and neck carcinogenesis. This material is unique as each panel of lesions is derived from the same patient and moreover we have previously assessed it for the DNA damage response (DDR) activation status. Since Beclin-1, LC3B and p62 reflect the nucleation, elongation and degradation stages of autophagy, respectively, their combined immunohistochemical (IHC) expression profiles could grossly mirror the autophagic flux. This experimental approach was further corroborated by ultrastructural analysis, applying transmission electron microscopy (TEM). The observed Beclin-1/LC3B/p62 IHC patterns, obtained from serial sections analysis, along with TEM findings are suggestive of a declined authophagic activity in preneoplastic lesions that was restored in full blown cancers. Correlating these findings with DDR status in the same pathological stages are indicative of: (i) an antitumor function of autophagy in support to that of DDR, possibly through energy deprivation in preneoplastic stages, thus preventing incipient cancer cells from evolving; and (ii) a tumor-supporting role in the cancerous stage. View Full-Text
Keywords: autophagy; Beclin-1; LC3B; p62; carcinogenesis; DNA damage response autophagy; Beclin-1; LC3B; p62; carcinogenesis; DNA damage response

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Havaki, S.; Vlachou, V.; Zampetidis, C.P.; Selemenakis, P.; Kotsinas, A.; Mavrogonatou, E.; Rizou, S.V.; Kyrodimos, E.; Evangelou, K.; Kletsas, D.; Giatromanolaki, A.; Gorgoulis, V.G. Monitoring Autophagy Immunohistochemically and Ultrastructurally during Human Head and Neck Carcinogenesis. Relationship with the DNA Damage Response Pathway. Int. J. Mol. Sci. 2017, 18, 1920.

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