title: WAVE1 regulates P-glycoprotein expression via Ezrin in leukemia cells.
abstract: For children with acute myeloblastic leukemia (AML), multidrug resistance (MDR) reduces treatment effectiveness, and often leads to poor patient survival. While a number of factors have been described that affect MDR, the mechanisms underlying this effect remain unclear. In this study, the role of WAVE1 in MDR was investigated. Among 62 children with AML, high levels of WAVE1 were associated with poor patient outcomes. Proteomic techniques were used to identify novel WAVE1-interacting proteins from leukemia cells, one of which was the cytoskeleton regulator Ezrin. In leukemia cells, WAVE1 co-localized with both Ezrin and P-glycoprotein (P-gp), a critical regulator of the MDR phenotype. Overexpression of WAVE1 in K562 leukemia cells up-regulated P-gp and Ezrin, and reduced K562 cells' sensitivity to the chemotherapy drug adriamycin. The opposite effect was seen when WAVE1 expression was reduced via RNA interference. Critically, overexpression of WAVE1 in the absence of Ezrin did not affect P-gp levels or MDR. These data suggest that WAVE1 affects P-gp and MDR of leukemia cells through Ezrin.
authors.affiliation: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan Province, People's Republic of China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Yang
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Zhao
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Kang
authors.forename: Yu-Lei
authors.initials: YL
authors.lastname: He
authors.forename: Xiao-Cheng
authors.initials: XC
authors.lastname: Yin
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Liu
authors.forename: Liang-Chun
authors.initials: LC
authors.lastname: Yang
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Zhan
authors.forename: Xiu-Shan
authors.initials: XS
authors.lastname: Wu
authors.forename: Dao-Lin
authors.initials: DL
authors.lastname: Tang
authors.forename: Li-Zhi
authors.initials: LZ
authors.lastname: Cao
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015153:Blotting, Western; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000502:physiology*; D000099149:Ezrin
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051300:Wiskott-Aldrich Syndrome Protein Family; D000099149:Ezrin; C114864:WASF1 protein, human