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

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.

Source: Molecular Cancer Research - February 27, 2017 Category: Cancer & Oncology Authors: Zhou, J., Chan, Z.-L., Bi, C., Lu, X., Chong, P. S. Y., Chooi, J.-Y., Cheong, L.-L., Liu, S.-C., Ching, Y. Q., Zhou, Y., Osato, M., Tan, T. Z., Ng, C. H., Ng, S.-B., Wang, S., Zeng, Q., Chng, W.-J. Tags: Oncogenes and Tumor Suppressors Source Type: research