NHE1 has a notable role in metastasis and drug resistance of T-cell acute lymphoblastic leukemia

Altaf,Ehtisham; Huang,Xiaoxing; Xiong,Jie; Yang,Xiangyong; Deng,Xinzhou; Xiong,Meng; Zhou,Lu; Pan,Shan; Yuan,Wen; Li,Xinran; Hao,Ling; Tembo,Kingsley  Miyanda; Xiao,Ruijing; Zhang,Qiuping

doi:10.3892/ol.2017.6716

NHE1 has a notable role in metastasis and drug resistance of T-cell acute lymphoblastic leukemia

Authors:
- Ehtisham Altaf
- Xiaoxing Huang
- Jie Xiong
- Xiangyong Yang
- Xinzhou Deng
- Meng Xiong
- Lu Zhou
- Shan Pan
- Wen Yuan
- Xinran Li
- Ling Hao
- Kingsley Miyanda Tembo
- Ruijing Xiao
- Qiuping Zhang
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Affiliations: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Bioengineering, Hubei University of Technology Engineering and Technology College, Wuhan, Hubei 430068, P.R. China, Department of Hematology, Taihe Hospital, Shiyan, Hubei 442000, P.R. China
Published online on: August 3, 2017 https://doi.org/10.3892/ol.2017.6716
Pages: 4256-4262

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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.

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