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- Title
NHE1 has a notable role in metastasis and drug resistance of T-cell acute lymphoblastic leukemia.
- Authors
ALTAF, EHTISHAM; XIAOXING HUANG; JIE XIONG; XIANGYONG YANG; XINZHOU DENG; MENG XIONG; LU ZHOU; SHAN PAN; WEN YUAN; XINRAN LI; LING HAO; TEMBO, KINGSLEY MIYANDA; RUIJING XIAO; QIUPING ZHANG
- Abstract
T-cell acute lymphoblastic leukemia (T-ALL) represents a spectrum of hematological malignancies that affect human health. Metastasis and chemotherapeutic drug resistance are the primary causes of mortality in patients with T-ALL. Sodium-hydrogen antiporter 1 (NHE1) is established to serve a role in metastasis and drug resistance in numerous types of cancer; however, the function of NHE1 in T-ALL remains to be elucidated. Previously, the C-C-motif chemokine ligand 25 (CCL25) was identified to be involved in metastasis and drug resistance in the MOLT4 T-ALL cell line, as was the ezrin protein. The present study investigated the role of NHE1 in the metastasis of T-ALL using a Transwell assay and scanning electron microscopy, using MOLT4 cells as a model. The association between NHE1 and ezrin was assessed using laser scanning confocal microscopy. The effect of NHE1 on resistance to the chemotherapy drug doxorubicin (DOX) was also investigated using a cell viability and cytotoxicity assay. Expression of NHE1 increased following treatment with CCL25, accompanied by morphological changes in MOLT4 cells and the co-localization of NHE1 with ezrin. In addition, wild-type MOLT4 cells exhibited an increased polarization ability compared with NHE1- or ezrin-silenced cells. NHE1- or ezrin-silenced cells exhibited higher sensitivity to DOX compared with wild-type MOLT4 cells. In conclusion, the increased expression or activity of NHE1 may potentially be a poor prognostic indicator for human T-ALL.
- Subjects
LYMPHOBLASTIC leukemia prognosis; SODIUM-hydrogen antiporter; DRUG resistance; GENE expression; CELL-mediated cytotoxicity
- Publication
Oncology Letters, 2017, Vol 14, Issue 4, p4256
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2017.6716