title: Cytosolic acetyl-CoA synthetase affected tumor cell  survival under hypoxia: the possible function in  tumor acetyl-CoA/acetate metabolism.
abstract: Understanding tumor-specific metabolism under hypoxia is important to find novel targets for antitumor drug design. Here we found that tumor cells expressed higher levels of cytosolic acetyl-CoA synthetase (ACSS2) under hypoxia than normoxia. Knockdown of ACSS2 by RNA interference (RNAi) in tumor cells enhanced tumor cell death under long-term hypoxia in vitro. Our data also demonstrated that the ACSS2 suppression slowed tumor growth in vivo. These findings showed that ACSS2 plays a significant role in tumor cell survival under hypoxia and that ACSS2 would be a potential target for tumor treatment. Furthermore, we found that tumor cells excreted acetate and the quantity increased under hypoxia: the pattern of acetate excretion followed the expression pattern of ACSS2. Additionally, the ACSS2 knockdown led to a corresponding reduction in the acetate excretion in tumor cells. These results mean that ACSS2 can conduct the reverse reaction from acetyl-CoA to acetate in tumor cells, which indicates that ACSS2 is a bi-directional enzyme in tumor cells and that ACSS2 might play a buffering role in tumor acetyl-CoA/acetate metabolism.
authors.affiliation: Biomedical Imaging Research Center, University of Fukui, 23-3, Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yoshii
authors.forename: Takako
authors.initials: T
authors.lastname: Furukawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshii
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mori
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kiyono
authors.forename: Atsuo
authors.initials: A
authors.lastname: Waki
authors.forename: Masato
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsujikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Okazawa
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Yonekura
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fujibayashi
mesh_terms: D000106:Acetate-CoA Ligase / Q000235:genetics / Q000378:metabolism*; D000085:Acetates / Q000378:metabolism*; D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival; D003600:Cytosol / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D034622:RNA Interference
chemical_list: D000085:Acetates; D000105:Acetyl Coenzyme A; D000106:Acetate-CoA Ligase