Phosphatase of regenerating liver-3 is expressed in acute lymphoblastic leukemia and mediates leukemic cell adhesion, migration and drug resistance.
Phosphatase of regenerating liver-3 is expressed in acute lymphoblastic leukemia and mediates leukemic cell adhesion, migration and drug resistance.
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DOI：
10.18632/oncotarget.23186
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发表时间：
2018-01-09
期刊：
影响因子：
--
通讯作者：
Rø TB
中科院分区：
文献类型：
--
作者：
Hjort MA;Abdollahi P;Vandsemb EN;Fenstad MH;Lund B;Slørdahl TS;Børset M;Rø TB
再生肝磷酸酶-3(PRL-3/PTP4A3)在多种肿瘤中表达上调，包括BCR-ABL1和ETV6-RUNX阳性的急性淋巴细胞白血病(ALL)。本研究旨在研究PRL-3在B细胞急性淋巴细胞白血病(B-ALL)中的生物学作用。在这里，我们证明，通过qRT-PCR或流式细胞仪检测，B-ALL细胞在mRNA和蛋白水平上的PRL-3表达高于正常细胞。此外，我们证明，使用shRNA或小分子抑制剂抑制Prl-3可以减少Preb-ALL细胞系REH和MHH-CALL-4中细胞向SDF-1α梯度的迁移。PRL-3基因敲除也减少了REH细胞对纤维连接蛋白的黏附。在机制上，PRL-3介导的SDF-1α刺激钙释放，并激活粘着斑激酶和sRc，它们是迁移和黏附的重要影响因素。PRL-3的表达使REH细胞对阿糖胞苷具有更强的耐药性。结论：B-ALL细胞中PRL-3的表达水平高于正常细胞。PRL-3促进细胞对阿糖胞苷的黏附、迁移和耐药性。PRL-3可能是治疗B-ALL的一个新靶点。
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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