Non-canonical activation of β-catenin by PRL-3 phosphatase in acute myeloid leukemia
| العنوان: | Non-canonical activation of β-catenin by PRL-3 phosphatase in acute myeloid leukemia |
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| المؤلفون: | Jayantha Gunaratne, Tuan Zea Tan, Jianbiao Zhou, Qi Zeng, Phyllis S.Y. Chong, Wee Joo Chng, Sabrina Hui Min Toh, Jing Yuan Chooi, Zit-Liang Chan, Sheena Wee |
| المصدر: | Oncogene. 38:1508-1519 |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Myeloid, Phosphatase, Biology, Proto-Oncogene Proteins c-myc, Mice, 03 medical and health sciences, Transactivation, 0302 clinical medicine, Cyclin D1, Genetics, medicine, Animals, Humans, Wnt Signaling Pathway, Molecular Biology, beta Catenin, Wnt signaling pathway, Myeloid leukemia, Xenograft Model Antitumor Assays, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Wnt Proteins, Leukemia, Myeloid, Acute, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Catenin, Cancer research, Protein Tyrosine Phosphatases, Signal transduction, Protein Binding, Transcription Factors |
| الوصف: | 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. |
| تدمد: | 1476-5594 0950-9232 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b1b5d3d75997594b4ed33183654d73d2 https://doi.org/10.1038/s41388-018-0526-3 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....b1b5d3d75997594b4ed33183654d73d2 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14765594 09509232 |
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