Home
Resources
Publications
Non-canonical Activation of β-catenin by PRL-3 Phosphatase in Acute Myeloid Leukemia

Non-canonical Activation of β-catenin by PRL-3 Phosphatase in Acute Myeloid Leukemia

Phyllis S Y Chong, Jianbiao Zhou, Jing-Yuan Chooi, Zit-Liang Chan, Sabrina Hui Min Toh, Tuan Zea Tan, Sheena Wee, Jayantha Gunaratne, Qi Zeng, Wee-Joo Chng

Oncogene. 2019 Feb;38(9):1508-1519.

PMID: 30305722

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP893449382	PRL-3 Inhibitor I		893449-38-2	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: