title: Carnitine transporter CT2 (SLC22A16) is over-expressed in acute myeloid leukemia (AML) and target knockdown reduces growth and viability of AML cells.
abstract: AML (acute myeloid leukemia) cells have a unique reliance on mitochondrial metabolism and fatty acid oxidation (FAO). Thus, blocking FAO is a potential therapeutic strategy to target these malignant cells. In the current study, we assessed plasma membrane carnitine transporters as novel therapeutic targets for AML. We examined the expression of the known plasma membrane carnitine transporters, OCTN1, OCTN2, and CT2 in AML cell lines and primary AML samples and compared expression to normal hematopoietic cells. Of the three carnitine transporters, CT2 demonstrated the greatest differential expression between AML and normal cells. Using shRNA, we knocked down CT2 and demonstrated that target knockdown impaired the function of the transporter. In addition, knockdown of CT2 reduced the growth and viability of AML cells with high expression of CT2 (OCI-AML2 and HL60), but not low expression. CT2 knockdown reduced basal oxygen consumption without a concomitant increase in glycolysis. Thus, CT2 may be a novel target for a subset of AML.
authors.affiliation: Princess Margaret Cancer Centre, Ontario Cancer Institute, 610 University Ave, Toronto, ON, M5G 2M9, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Rose
authors.initials: R
authors.lastname: Hurren
authors.forename: Neil
authors.initials: N
authors.lastname: MacLean
authors.forename: Marcela
authors.initials: M
authors.lastname: Gronda
authors.forename: Yulia
authors.initials: Y
authors.lastname: Jitkova
authors.forename: Mahadeo A
authors.initials: MA
authors.lastname: Sukhai
authors.forename: Mark D
authors.initials: MD
authors.lastname: Minden
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Schimmer
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D055785:Gene Knockdown Techniques; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D027701:Organic Cation Transport Proteins; D034741:RNA, Small Interfering; C467737:SLC22A16 protein, human; D010100:Oxygen