Abstract：
:Altered metabolism is considered as a hallmark of cancer. Here we investigated expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) 2 lyase (HMGCL), an essential enzyme in ketogenesis, which produces ketone bodies by the breakdown of fatty acids to supply energy, in nasopharyngeal carcinoma (NPC). The expression of HMGCL was silenced in NPC tissue. Downregulation of HMGCL in NPC was associated with low intracellular β-hydroxybutyrate (β-HB) production, thereby reducing reactive oxygen species (ROS) generation. Ectopic expression of HMGCL restored β-HB level, associated with suppressed proliferation and colony formation of NPC cells in vitro and decreased tumorigenicity in vivo. HMGCL suppressed the migration and invasion of NPC cells in vitro via mesenchymal-epithelial transition. Furthermore, extracellular β-HB supply suppressed the proliferation and migration of NPC cells. Both intra- and extracellular β-HB exerting a suppressive role in NPC depends on ROS generation. Ketogenesis may be impaired in NPC cells due to lack of HMGCL expression, suggesting that it may be a promising target in NPC therapy.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Luo W,Qin L,Li B,Liao Z,Liang J,Xiao X,Xiao X,Mo Y,Huang G,Zhang Z,Zhou X,Li Pdoi
10.1038/s41598-017-11025-2subject
Has Abstractpub_date
2017-09-20 00:00:00pages
11954issue
1issn
2045-2322pii
10.1038/s41598-017-11025-2journal_volume
7pub_type
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