The pro-metastasis tyrosine phosphatase, PRL-3 (PTP4A3), is a novel mediator of oncogenic function of BCR-ABL in human chronic myeloid leukemia

Molecular Cancer

Short Communication

Jianbiao Zhou¹  Sylvia Mahara¹  Phyllis SY Chong¹  Kelly OK Ong¹  Shaw-Cheng Liu¹  Chonglei Bi¹  Wee Joo Chng²  Lip-Lee Cheong³  Qi Zeng⁴ 

[1] Cancer Science Institute of Singapore, Singapore, Singapore;Cancer Science Institute of Singapore, Singapore, Singapore;Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;Department of Hematology-Oncology, National University Hospital, Singapore, Singapore;Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;Institute of Molecular and Cell Biology (IMCB), A*Star, Singapore, Singapore;

关键词: Chronic myeloid leukemia (CML);    Protein-tyrosine phosphatase of regenerating liver 3 (PRL-3);    PTP4A3;    BCR-ABL;    Imatinib;    Tyrosine kinase inhibitor (TKI);   

DOI  :  10.1186/1476-4598-11-72

 received in 2012-07-02, accepted in 2012-09-14,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundResistance to tyrosine kinase inhibitors (TKIs) remains a challenge in management of patients with chronic myeloid leukemia (CML). A better understanding of the BCR-ABL signalling network may lead to better therapy.FindingsHere we report the discovery of a novel downstream target of BCR-ABL signalling, PRL-3 (PTP4A3), an oncogenic tyrosine phosphatase. Analysis of CML cancer cell lines and CML patient samples reveals the upregulation of PRL-3. Inhibition of BCR-ABL signalling either by Imatinib or by RNAi silencing BCR-ABL reduces PRL-3 and increases cleavage of PARP. In contrast, the amount of PRL-3 protein remains constant or even increased in response to Imatinib treatment in drug resistant cells expressing P210 T315I. Finally, analysis with specific shRNA shows PRL-3 involvement in the proliferation and self-renewal of CML cells.ConclusionsThese data support a role for PRL-3 in BCR-ABL signalling and CML biology and may be a potential therapeutic target downstream of BCR-ABL in TKI resistant mutant cells.

【 授权许可】

Unknown   
© Zhou et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.