Open Access

EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway

  • Authors:
    • Rui Huang
    • Huimin Liu
    • Yiran Chen
    • Yanjie He
    • Qian Kang
    • Sanfang Tu
    • Yingzhi He
    • Xuan Zhou
    • Lei Wang
    • Jilong Yang
    • Anqin Wu
    • Yuhua Li
  • View Affiliations

  • Published online on: November 20, 2017     https://doi.org/10.3892/or.2017.6102
  • Pages:119-128
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although the introduction of tyrosine kinase inhibitors greatly improved the survival of patients with chronic myeloid leukemia (CML), drug resistance remains a problem. Thus, mechanism-based novel therapeutic targets warrant exploration. Recently, epidermal growth factor receptor kinase substrate 8 (EPS8), which has been identified as an oncogene and plays an important role in a broad spectrum of solid tumours, was reported to be related to poor prognosis or chemoresistance in acute leukemia patients. However, its role in CML remains unclear. In the present study, using q-RT‑PCR, we demonstrated that CML patients expressed a higher level of EPS8 mRNA in bone marrow mononuclear cells than healthy controls. Then, to determine the effect of EPS8 on the biological functions of CML cells, EPS8 expression was knocked down in the human CML cell line K562. Reduced proliferation, increased apoptosis, impaired adhesion and migration were observed in K562 cells after EPS8 silencing. Notably, attenuation of EPS8 increased chemosensitivity both in imatinib-sensitive K562 cells and in the imatinib-resistant murine BCR-ABL+ 32D-p210BCR/ABL-T315I cells. Mechanistically, knockdown of EPS8 downregulated p-BCR/ABL and its downstream AKT/mTOR signalling pathway. Finally, knockdown of EPS8 attenuated K562 cell proliferation in BALB/c nude mice. These data indicated that EPS8 regulated the proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway. Targeting EPS8 alone or combined with a tyrosine kinase inhibitor may be a promising alternative therapeutic strategy.

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January 2018
Volume 39 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

2016 Impact Factor: 2.662
Ranked #31/217 Oncology
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APA
Huang, R., Liu, H., Chen, Y., He, Y., Kang, Q., Tu, S. ... Li, Y. (2018). EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway. Oncology Reports, 39, 119-128. https://doi.org/10.3892/or.2017.6102
MLA
Huang, R., Liu, H., Chen, Y., He, Y., Kang, Q., Tu, S., He, Y., Zhou, X., Wang, L., Yang, J., Wu, A., Li, Y."EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway". Oncology Reports 39.1 (2018): 119-128.
Chicago
Huang, R., Liu, H., Chen, Y., He, Y., Kang, Q., Tu, S., He, Y., Zhou, X., Wang, L., Yang, J., Wu, A., Li, Y."EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway". Oncology Reports 39, no. 1 (2018): 119-128. https://doi.org/10.3892/or.2017.6102