LIN28B Activation by PRL-3 Promotes Leukemogenesis and a Stem Cell-like Transcriptional Program in AML.

Autor:	Zhou J; 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., Chan ZL; Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore., Bi C; Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore., Lu X; Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore., Chong PS; Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore., Chooi JY; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore., Cheong LL; Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore., Liu SC; Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore., Ching YQ; Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore., Zhou Y; Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore., Osato M; Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore., Tan TZ; Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore., Ng CH; Department of Haematology-Oncology, National University Cancer Institute, NUHS, Singapore, Republic of Singapore., Ng SB; 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., Wang S; Department of Pathology, National University Hospital, National University Health System, Singapore., Zeng Q; Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Singapore, Republic of Singapore., Chng WJ; 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.
Jazyk:	angličtina
Zdroj:	Molecular cancer research : MCR [Mol Cancer Res] 2017 Mar; Vol. 15 (3), pp. 294-303. Date of Electronic Publication: 2016 Dec 23.
DOI:	10.1158/1541-7786.MCR-16-0275-T
Abstrakt:	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 leukemogenesis in vitro and in vivo Furthermore, 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 . (©2016 American Association for Cancer Research.)
Databáze:	MEDLINE
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