title: LIN28B Activation by PRL-3 Promotes Leukemogenesis and a Stem Cell-like Transcriptional Program in AML.
abstract: PRL-3 (PTP4A3), a metastasis-associated phosphatase, is also upregulated in patients with acute myeloid leukemia (AML) and is associated with poor prognosis, but the underlying molecular mechanism is unknown. Here, constitutive expression of PRL-3 in human AML cells sustains leukemogenesisin vitroandin vivoFurthermore, PRL-3 phosphatase activity dependently upregulates LIN28B, a stem cell reprogramming factor, which in turn represses the let-7 mRNA family, inducing a stem cell-like transcriptional program. Notably, elevated levels of LIN28B protein independently associate with worse survival in AML patients. Thus, these results establish a novel signaling axis involving PRL-3/LIN28B/let-7, which confers stem cell-like properties to leukemia cells that is important for leukemogenesis.Implications:The current study offers a rationale for targeting PRL-3 as a therapeutic approach for a subset of AML patients with poor prognosis.Mol Cancer Res; 15(3); 294-303. ©2016 AACR.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Jianbiao
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
authors.forename: Zit-Liang
authors.initials: ZL
authors.lastname: Chan
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
authors.forename: Chonglei
authors.initials: C
authors.lastname: Bi
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lu
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
authors.forename: Phyllis S Y
authors.initials: PS
authors.lastname: Chong
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Chooi
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
authors.forename: Lip-Lee
authors.initials: LL
authors.lastname: Cheong
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
authors.forename: Shaw-Cheng
authors.initials: SC
authors.lastname: Liu
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
authors.forename: Ying Qing
authors.initials: YQ
authors.lastname: Ching
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
authors.forename: Motomi
authors.initials: M
authors.lastname: Osato
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
authors.forename: Tuan Zea
authors.initials: TZ
authors.lastname: Tan
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute, NUHS, Singapore, Republic of Singapore.
authors.forename: Chin Hin
authors.initials: CH
authors.lastname: Ng
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.|Department of Pathology, National University Hospital, Singapore, Republic of Singapore.|Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Siok-Bian
authors.initials: SB
authors.lastname: Ng
authors.affiliation: Department of Pathology, National University Hospital, National University Health System, Singapore.
authors.forename: Shi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Singapore, Republic of Singapore.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore. mdccwj@nus.edu.sg.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.|Department of Haematology-Oncology, National University Cancer Institute, NUHS, Singapore, Republic of Singapore.
authors.forename: Wee-Joo
authors.initials: WJ
authors.lastname: Chng
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; C516326:LIN28B protein, human; C570876:Lin28b protein, mouse; D009363:Neoplasm Proteins; C111534:Ptp4a3 protein, mouse; D016601:RNA-Binding Proteins; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases