title: The pro-metastasis tyrosine phosphatase, PRL-3 (PTP4A3), is a novel mediator of oncogenic function of BCR-ABL in human chronic myeloid leukemia.
abstract: BACKGROUND
  Resistance 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.
  
  
  RESULTS
  Here 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Cancer Science Institute of Singapore, Singapore, Singapore.
authors.forename: Jianbiao
authors.initials: J
authors.lastname: Zhou
authors.forename: Lip-Lee
authors.initials: LL
authors.lastname: Cheong
authors.forename: Shaw-Cheng
authors.initials: SC
authors.lastname: Liu
authors.forename: Phyllis S Y
authors.initials: PS
authors.lastname: Chong
authors.forename: Sylvia
authors.initials: S
authors.lastname: Mahara
authors.forename: Chonglei
authors.initials: C
authors.lastname: Bi
authors.forename: Kelly Ok
authors.initials: KO
authors.lastname: Ong
authors.forename: Qi
authors.initials: Q
authors.lastname: Zeng
authors.forename: Wee Joo
authors.initials: WJ
authors.lastname: Chng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic; D020868:Gene Silencing; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics*; D011743:Pyrimidines / Q000494:pharmacology; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009363:Neoplasm Proteins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D050791:STAT Transcription Factors; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases