Τίτλος:
Monitoring autophagy immunohistochemically and ultrastructurally during human head and neck carcinogenesis. Relationship with the DNA damage response pathway
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
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.
Περιοδικό:
International Journal of Molecular Sciences
Λέξεις-κλειδιά:
beclin 1; cyclin dependent kinase; mammalian target of rapamycin; microtubule associated protein 1; promyelocytic leukemia protein; RING finger protein; RING finger protein 168; sequestosome 1; sirtuin 1; transcription factor Nrf2; unclassified drug; beclin 1, antineoplastic activity; Article; autophagy; carcinogenesis; cell proliferation; clinical article; controlled study; DNA damage response; double stranded DNA break; gene expression profiling; head and neck carcinoma; human; human tissue; immunohistochemistry; nuclear export signal; protein degradation; transcription regulation; transmission electron microscopy; ultrastructure; autophagy; DNA damage; genetics; head and neck tumor; immunohistochemistry; metabolism; physiology; procedures, Autophagy; Beclin-1; DNA Damage; Head and Neck Neoplasms; Humans; Immunohistochemistry
DOI:
10.3390/ijms18091920
