Increased NEK2 in hepatocellular carcinoma promotes cancer progression and drug resistance by promoting PP1/Akt and Wnt activation

Wen,Sailan; Liu,Yuwu; Yang,Manyi; Yang,Keda; Huang,Jianghai; Feng,Deyun

doi:10.3892/or.2016.5009

Increased NEK2 in hepatocellular carcinoma promotes cancer progression and drug resistance by promoting PP1/Akt and Wnt activation

Authors:
- Sailan Wen
- Yuwu Liu
- Manyi Yang
- Keda Yang
- Jianghai Huang
- Deyun Feng
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Affiliations: Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Morphology, The Institute of Advanced Occupation Technology, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, National Hepatobiliary and Enteric Surgery Research Center, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: August 9, 2016 https://doi.org/10.3892/or.2016.5009
Pages: 2193-2199

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Abstract

NIMA-related expressed kinase 2 (NEK2) participates in the carcinogenesis and progression of certain types of cancer, however, its expression and roles in the development of hepatocellular carcinoma (HCC) remains unknown. Here, we found that NEK2 expression was significantly upregulated in both human HCC tissues and cell lines, and increased NEK2 expression in HCC was significantly correlated with clinical progression of HCC in patients. Knockdown of NEK2 in HCC cells inhibited HCC progression, as determined by the suppressed cell proliferation, invasion and metastasis. Furthermore, knockdown of NEK2 inhibited drug resistance of HCC cells, as shown by the promoted suppression of cell viability in 5-fluorouracil (5‑FU)‑treated HCC cells. Mechanistically, protein phosphatase 1 (PP1)/Akt and Wnt signaling activation are significantly inhibited by NEK2 knockdown, which is responsible for the HCC progression and involved in NEK2‑induced cancer cell abnormal biological behavior. Thus, enhanced NEK2 expression in HCC promotes HCC progression and drug resistance by promoting PP1/Akt and Wnt pathway activation, which may represent a new therapeutic target for HCC.

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