LIN28B Activation by PRL-3 Promotes Leukemogenesis and a Stem Cell–like Transcriptional Program in AML
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- Chonglei Bi
- 1Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
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- Zit-Liang Chan
- 1Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
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- Jianbiao Zhou
- 1Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
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- Xiao Lu
- 1Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
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- Phyllis S.Y. Chong
- 1Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
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- Jing-Yuan Chooi
- 2Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.
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- Shaw-Cheng Liu
- 1Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
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- Lip-Lee Cheong
- 1Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
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- Tuan Zea Tan
- 1Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
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- Chin Hin Ng
- 3Department of Haematology-Oncology, National University Cancer Institute, NUHS, Singapore, Republic of Singapore.
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- Siok-Bian Ng
- 1Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
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- Qi Zeng
- 5Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Singapore, Republic of Singapore.
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- Shi Wang
- 7Department of Pathology, National University Hospital, National University Health System, Singapore.
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- Wee-Joo Chng
- 1Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
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- Ying Qing Ching
- 1Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
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- Motomi Osato
- 1Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
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- Yafeng Zhou
- 1Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
書誌事項
- 公開日
- 2017-02-28
- 資源種別
- journal article
- DOI
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- 10.1158/1541-7786.mcr-16-0275-t
- 公開者
- American Association for Cancer Research (AACR)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>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.</jats:p> <jats:p>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.</jats:p>
収録刊行物
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- Molecular Cancer Research
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Molecular Cancer Research 15 (3), 294-303, 2017-02-28
American Association for Cancer Research (AACR)
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詳細情報 詳細情報について
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- CRID
- 1360004236376433792
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- ISSN
- 15573125
- 15417786
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
