Phosphatase of regenerating liver-3 is expressed in acute lymphoblastic leukemia and mediates leukemic cell adhesion, migration and drug resistance
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Magnus A. Hjort1,2, Pegah Abdollahi1,3, Esten N. Vandsemb1,3, Mona H. Fenstad1,3, Bendik Lund1,2, Tobias S. Slørdahl1,4, Magne Børset1,3 and Torstein B. Rø1,2
1Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
2Children’s Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
3Department of Immunology and Transfusion Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
4Department of Hematology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
Magnus A. Hjort, email: [email protected]
Keywords: PRL-3; acute lymphoblastic leukemia; migration; adhesion; drug resistance
Received: October 11, 2017 Accepted: December 01, 2017 Published: December 13, 2017
Phosphatase of regenerating liver-3 (PRL-3/PTP4A3) is upregulated in multiple cancers, including BCR-ABL1- and ETV6-RUNX-positive acute lymphoblastic leukemia (ALL). With this study, we aim to characterize the biological role of PRL-3 in B cell ALL (B-ALL). Here, we demonstrate that PRL-3 expression at mRNA and protein level was higher in B-ALL cells than in normal cells, as measured by qRT-PCR or flow cytometry. Further, we demonstrate that inhibition of PRL-3 using shRNA or a small molecular inhibitor reduced cell migration towards an SDF-1α gradient in the preB-ALL cell lines Reh and MHH-CALL-4. Knockdown of PRL-3 also reduced cell adhesion towards fibronectin in Reh cells. Mechanistically, PRL-3 mediated SDF-1α stimulated calcium release, and activated focal adhesion kinase (FAK) and Src, important effectors of migration and adhesion. Finally, PRL-3 expression made Reh cells more resistance to cytarabine treatment. In conclusion, the expression level of PRL-3 was higher in B-ALL cells than in normal cells. PRL-3 promoted adhesion, migration and resistance to cytarabine. PRL-3 may represent a novel target in the treatment of B-ALL.
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