ID 52006
JaLCDOI
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Author
Tazawa, Hiroshi ORCID Kakenhi
Kagawa, Shunsuke ORCID Kakenhi
Fujiwara, Toshiyoshi ORCID Kakenhi
Abstract
Autophagy is a catabolic process that produces energy through lysosomal degradation of intracellular organelles. Autophagy functions as a cytoprotective factor under physiological conditions such as nutrient deprivation, hypoxia, and interruption of growth factors. On the other hand, infection with pathogenic viruses and bacteria also induces autophagy in infected cells. Oncolytic virotherapy with replication-competent viruses is thus a promising strategy to induce tumor-specific cell death. Oncolytic adenoviruses induce autophagy and subsequently contribute to cell death rather than cell survival in tumor cells. We previously developed a telomerase-specific replication-competent oncolytic adenovirus, OBP-301, which induces cell lysis in tumor cells with telomerase activities. OBP-301-mediated cytopathic activity is significantly associated with induction of autophagy biomarkers. In this review, we focus on the tumor-suppressive role and molecular basis of autophagic machinery induced by oncolytic adenoviruses. Addition of tumor-specific promoters and modification of the fiber knob of adenoviruses supports the oncolytic adenovirus-mediated autophagic cell death. Autophagy is cooperatively regulated by the E1-dependent activation pathway, E4-dependent inhibitory pathway, and microRNA-dependent fine-tuning. Thus, future exploration of the functional role and molecular mechanisms underlying oncolytic adenovirus-induced autophagy would provide novel insights and improve the therapeutic potential of oncolytic adenoviruses.
Keywords
oncolytic adenovirus
autophagy
E2F1
microRNA
Amo Type
Review
Published Date
2013-12
Publication Title
Acta Medica Okayama
Volume
volume67
Issue
issue6
Publisher
Okayama University Medical School
Start Page
333
End Page
342
ISSN
0386-300X
NCID
AA00508441
Content Type
Journal Article
language
英語
Copyright Holders
CopyrightⒸ 2013 by Okayama University Medical School
File Version
publisher
Refereed
True
PubMed ID
Web of Sience KeyUT