NLK interacts with 14‑3‑3ζ to restore the expression of E‑cadherin

Chen,Jie; Lin,Qingfeng; Ni,Tingting; Zhao,Jiyi; Lin,Feng; Lu,Xiangdong; Lv,Ye; Ren,Shujuan; Liu,Zhili; Zhang,Ting; He,Shuyan; Shen,Dong; Mao,Weidong

doi:10.3892/or.2020.7557

NLK interacts with 14‑3‑3ζ to restore the expression of E‑cadherin

Authors:
- Jie Chen
- Qingfeng Lin
- Tingting Ni
- Jiyi Zhao
- Feng Lin
- Xiangdong Lu
- Ye Lv
- Shujuan Ren
- Zhili Liu
- Ting Zhang
- Shuyan He
- Dong Shen
- Weidong Mao
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Affiliations: Department of Oncology, The Jiangyin Clinical College of Xuzhou Medical University, Wuxi, Jiangsu 214400, P.R. China, Department of Oncology, Nantong Tumor Hospital, Nantong, Jiangsu 226001, P.R. China, Department of Gastroenterology, The Jiangyin Clinical College of XuZhou Medical University, Wuxi, Jiangsu 214400, P.R. China, Department of Central Laboratory, The Jiangyin Clinical College of XuZhou Medical University, Wuxi, Jiangsu 214400, P.R. China
Published online on: March 20, 2020 https://doi.org/10.3892/or.2020.7557
Pages: 1845-1852
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The Nemo‑like kinase (NLK), a conserved serine/threonine kinase, plays a critical role in the regulation of a variety of transcription factors, with important roles in determining cell fate. Although recent studies have demonstrated decreased expression patterns of NLK in various types of human cancer, the functional mechanism of NLK in cancer development has not been elucidated. Here, in the present study overexpression of NLK was found to inhibit the growth and migration of the non‑small cell lung cancer A549 cell line. NLK was subsequently found to interact with 14‑3‑3ζ (also known as YWHAZ), which is responsible for E‑cadherin silencing during epithelial‑mesenchymal transition (EMT). Furthermore, NLK overexpression was able to restore the expression of E‑cadherin inhibited by 14‑3‑3ζ. Notably, NLK interacts with 14‑3‑3ζ and prevents its dimerization, which is essential for 14‑3‑3ζ stability and function. By fusing two copies of the 14‑3‑3ζ gene, via a Gly‑rich linker, a non‑dissociable dimer of 14‑3‑3ζ was formed. It was found that NLK was unable to restore the expression of E‑cadherin inhibited by the overexpression of the fused dimer of 14‑3‑3ζ. In addition, the increased ability of migration induced by the overexpression of fused 14‑3‑3ζ dimer could not be altered by NLK overexpression. The results from the present study indicate that NLK is a negative regulator of 14‑3‑3ζ and plays a tumor suppressive role in the inhibition of cancer cell migration.

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