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

被引:8
作者
Havaki, Sophia [1 ]
Vlachou, Vassiliki [1 ]
Zampetidis, Christos P. [1 ]
Selemenakis, Platonas [1 ]
Kotsinas, Athanassios [1 ]
Mavrogonatou, Eleni [2 ]
Rizou, Sophia V. [1 ]
Kyrodimos, Euthymios [3 ]
Evangelou, Konstantinos [1 ]
Kletsas, Dimitris [2 ]
Giatromanolaki, Alexandra [4 ]
Gorgoulis, Vassilis G. [1 ,5 ,6 ]
机构
[1] Natl & Kapodistrian Univ Athens, Sch Med, Dept Histol & Embryol, Mol Carcinogenesis Grp, 75 Mikras Asias St, Athens 11527, Greece
[2] Natl Ctr Sci Res Demokritos, Inst Biosci & Applicat, Lab Cell Proliferat & Ageing, Athens 15310, Greece
[3] Natl & Kapodistrian Univ Athens, Hippokrat Gen Hosp, Dept Otolaryngol Head & Neck Surg, 114 Queen Sofia Ave, Athens 11527, Greece
[4] Democritus Univ Thrace, Sch Med, Dept Pathol, Alexandroupolis 68100, Greece
[5] Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Inst Canc Sci, Manchester MP13 9PL, Lancs, England
[6] Acad Athens, Biomed Res Fdn, 4 Soranou Ephessiou St, Athens 11527, Greece
关键词
autophagy; Beclin-1; LC3B; p62; carcinogenesis; DNA damage response; REGULATES CHROMATIN UBIQUITINATION; ONCOGENE-INDUCED SENESCENCE; BECLIN; GENOMIC INSTABILITY; NUCLEAR LC3; DISEASE; STRESS; EXPRESSION; CELLS; P62;
D O I
10.3390/ijms18091920
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页数:17
相关论文
共 69 条
[1]   Autophagy: A boon or bane in oral cancer [J].
Adhauliya, Namrata ;
Kalappanavar, Anupama N. ;
Ali, I. M. ;
Annigeri, Rajeshwari G. .
ORAL ONCOLOGY, 2016, 61 :120-126
[2]   Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints [J].
Bartkova, Jirina ;
Rezaei, Nousin ;
Liontos, Michalis ;
Karakaidos, Panagiotis ;
Kletsas, Dimitris ;
Issaeva, Natalia ;
Vassiliou, Leandros-Vassilios F. ;
Kolettas, Evangelos ;
Niforou, Katerina ;
Zoumpourlis, Vassilis C. ;
Takaoka, Munenori ;
Nakagawa, Hiroshi ;
Tort, Frederic ;
Fugger, Kasper ;
Johansson, Fredrik ;
Sehested, Maxwell ;
Andersen, Claus L. ;
Dyrskjot, Lars ;
Orntoft, Torben ;
Lukas, Jiri ;
Kittas, Christos ;
Helleday, Thomas ;
Halazonetis, Thanos D. ;
Bartek, Jiri ;
Gorgoulis, Vassilis G. .
NATURE, 2006, 444 (7119) :633-637
[3]  
Carden DL, 2000, J PATHOL, V190, P255, DOI 10.1002/(SICI)1096-9896(200002)190:3<255::AID-PATH526>3.0.CO
[4]  
2-6
[5]   Simultaneous activation and inhibition of autophagy sensitizes cancer cells to chemotherapy [J].
Chi, Kwan-Hwa ;
Wang, Yu-Shan ;
Huang, Yi-Chun ;
Chiang, Hsin-Chien ;
Chi, Mau-Shin ;
Chi, Chau-Hwa ;
Wang, Hsin-Ell ;
Kao, Shang-Jyh .
ONCOTARGET, 2016, 7 (36) :58075-58088
[6]  
Choi AMK, 2013, NEW ENGL J MED, V368, P1845, DOI [10.1056/NEJMra1205406, 10.1056/NEJMc1303158]
[7]   The role of autophagy in squamous cell carcinoma of the head and neck [J].
Cosway, Benjamin ;
Lovat, Penny .
ORAL ONCOLOGY, 2016, 54 :1-6
[8]   Chaperone-mediated autophagy: roles in disease and aging [J].
Cuervo, Ana Maria ;
Wong, Esther .
CELL RESEARCH, 2014, 24 (01) :92-104
[9]   Nucleocytoplasmic Distribution and Dynamics of the Autophagosome Marker EGFP-LC3 [J].
Drake, Kimberly R. ;
Kang, Minchul ;
Kenworthy, Anne K. .
PLOS ONE, 2010, 5 (03)
[10]   The DNA damage checkpoint precedes activation of ARF in response to escalating oncogenic stress during tumorigenesis [J].
Evangelou, K. ;
Bartkova, J. ;
Kotsinas, A. ;
Pateras, I. S. ;
Liontos, M. ;
Velimezi, G. ;
Kosar, M. ;
Liloglou, T. ;
Trougakos, I. P. ;
Dyrskjot, L. ;
Andersen, C. L. ;
Papaioannou, M. ;
Drosos, Y. ;
Papafotiou, G. ;
Hodny, Z. ;
Sosa-Pineda, B. ;
Wu, X-R ;
Klinakis, A. ;
Orntoft, T. ;
Lukas, J. ;
Bartek, J. ;
Gorgoulis, V. G. .
CELL DEATH AND DIFFERENTIATION, 2013, 20 (11) :1485-1497