E3 ubiquitin ligase Hakai regulates cell growth and invasion, and increases the chemosensitivity to cisplatin in non‑small‑cell lung cancer cells

Liu,Zi; Wu,Yuqing; Tao,Zijian; Ma,Liang

doi:10.3892/ijmm.2018.3683

E3 ubiquitin ligase Hakai regulates cell growth and invasion, and increases the chemosensitivity to cisplatin in non‑small‑cell lung cancer cells

Authors:
- Zi Liu
- Yuqing Wu
- Zijian Tao
- Liang Ma
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Affiliations: Department of Chemical Biology and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma'anshan, Anhui 243002, P.R. China, Department of Pathology, Ma'anshan Municipal People's Hospital, Ma'anshan, Anhui 243000, P.R. China
Published online on: May 17, 2018 https://doi.org/10.3892/ijmm.2018.3683
Pages: 1145-1151

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Abstract

Hakai was originally identified as an E3 ubiquitin ligase of the E‑cadherin complex implicated in cell adhesion and invasion. Recently, emerging evidence has strongly suggested that Hakai serves a pivotal role in the tumorigenesis of certain tumors. However, the role of Hakai in non‑small‑cell lung cancer (NSCLC) and its underlying molecular mechanism have not been clarified. In the present study, it was observed that Hakai was highly expressed in NSCLC cell lines compared with human normal bronchial epithelial cells, and transfection with Hakai small interfering RNA significantly inhibited the growth of A549 and NCI‑H460 NSCLC cells. In addition, the inhibition of Hakai suppressed NSCLC cell migration and invasion through upregulation of E‑cadherin and downregulation of N‑cadherin. Notably, it was also revealed that knockdown of Hakai led to a decrease in the expression of phosphorylated AKT (Ser473), and a significant enhancement of chemosensitivity to cisplatin was observed following Hakai suppression. In conclusion, the present study demonstrated for the first time that knockdown of Hakai inhibited the proliferation, migration and invasion of NSCLC cells, and sensitized NSCLC cells to cisplatin. Thus, Hakai may serve as a potential therapeutic target for the treatment of NSCLC.

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