| Literature DB >> 28011885 |
Jianbiao Zhou1,2, Zit-Liang Chan1, Chonglei Bi1, Xiao Lu1, Phyllis S Y Chong1, Jing-Yuan Chooi2, Lip-Lee Cheong1, Shaw-Cheng Liu1, Ying Qing Ching1, Yafeng Zhou1, Motomi Osato1, Tuan Zea Tan1, Chin Hin Ng3, Siok-Bian Ng1,4,5, Shi Wang6, Qi Zeng7, Wee-Joo Chng8,2,3.
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 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.Entities:
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Year: 2016 PMID： 28011885 DOI： 10.1158/1541-7786.MCR-16-0275-T
Source DB: PubMed Journal: Mol Cancer Res ISSN： 1541-7786 Impact factor: 5.852