Phosphatase of regenerating liver-3 is expressed in acute lymphoblastic leukemia and mediates leukemic cell adhesion, migration and drug resistance
| العنوان: | Phosphatase of regenerating liver-3 is expressed in acute lymphoblastic leukemia and mediates leukemic cell adhesion, migration and drug resistance |
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| المؤلفون: | Tobias S. Slørdahl, Mona H. Fenstad, Pegah Abdollahi, Bendik Lund, Esten Nymoen Vandsemb, Magnus Aassved Hjort, Magne Børset, Torstein Baade Rø |
| المصدر: | Oncotarget OncoTarget |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, endocrine system, acute lymphoblastic leukemia, migration, Flow cytometry, Focal adhesion, 03 medical and health sciences, 0302 clinical medicine, medicine, Cell adhesion, B cell, drug resistance, biology, medicine.diagnostic_test, Chemistry, Cell migration, Fibronectin, adhesion, 030104 developmental biology, medicine.anatomical_structure, Oncology, Cell culture, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Cytarabine, PRL-3, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Research Paper |
| الوصف: | 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. Copyright: Hjort et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| تدمد: | 1949-2553 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f0071daa3999c1e63a67ff612f65118Test https://pubmed.ncbi.nlm.nih.gov/29423065Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0f0071daa3999c1e63a67ff612f65118 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19492553 |
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