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

Huang,Rui; Liu,Huimin; Chen,Yiran; He,Yanjie; Kang,Qian; Tu,Sanfang; He,Yingzhi; Zhou,Xuan; Wang,Lei; Yang,Jilong; Wu,Anqin; Li,Yuhua

doi:10.3892/or.2017.6102

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
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Affiliations: Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China
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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