Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41388-018-0526-3
Title: Non-canonical activation of beta-catenin by PRL-3 phosphatase in acute myeloid leukemia
Authors: Chong, Phyllis SY 
Zhou, Jianbiao 
Chooi, Jing-Yuan 
Chan, Zit-Liang
Toh, Sabrina Hui Min 
Tan, Tuan Zea 
Wee, Sheena
Gunaratne, Jayantha 
Zeng, Qi 
Chng, Wee-Joo 
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Oncology
Cell Biology
Genetics & Heredity
SIGNALING PATHWAY
ASSOCIATION
Issue Date: 28-Feb-2019
Publisher: NATURE PUBLISHING GROUP
Citation: Chong, Phyllis SY, Zhou, Jianbiao, Chooi, Jing-Yuan, Chan, Zit-Liang, Toh, Sabrina Hui Min, Tan, Tuan Zea, Wee, Sheena, Gunaratne, Jayantha, Zeng, Qi, Chng, Wee-Joo (2019-02-28). Non-canonical activation of beta-catenin by PRL-3 phosphatase in acute myeloid leukemia. ONCOGENE 38 (9) : 1508-1519. ScholarBank@NUS Repository. https://doi.org/10.1038/s41388-018-0526-3
Abstract: © 2018, Springer Nature Limited. Aberrant activation of Wnt/β-catenin signaling pathway is essential for the development of AML; however, the mechanistic basis for this dysregulation is unclear. PRL-3 is an oncogenic phosphatase implicated in the development of LSCs. Here, we identified Leo1 as a direct and specific substrate of PRL-3. Serine-dephosphorylated form of Leo1 binds directly to β-catenin, promoting the nuclear accumulation of β-catenin and transactivation of TCF/LEF downstream target genes such as cyclin D1 and c-myc. Importantly, overexpression of PRL-3 in AML cells displayed enhanced sensitivity towards β-catenin inhibition in vitro and in vivo, suggesting that these cells are addicted to β-catenin signaling. Altogether, our study revealed a novel regulatory role of PRL-3 in the sustenance of aberrant β-catenin signaling in AML. PRL-3 may serve as a biomarker to select for the subset of AML patients who are likely to benefit from treatment with β-catenin inhibitors. Our study presents a new avenue of cancer inhibition driven by PRL-3 overexpression or β-catenin hyperactivation.
Source Title: ONCOGENE
URI: https://scholarbank.nus.edu.sg/handle/10635/166529
ISSN: 09509232
14765594
DOI: 10.1038/s41388-018-0526-3
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