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Cited by 414-3-3 protein interactionsMechanisms of cancer metastasisCancer Cells and Metastasis

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

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Chen, Jie, Lin, Qingfeng, Ni, Tingting, Zhao, Jiyi, Lin, Feng, Lu, Xiangdong, Lv, Ye, Ren, Shujuan +5 more·2020·Oncology Reports
DOI 10.3892/or.2020.7557PMC PMC7160556
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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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  • NLK interacts with 14-3-3ζ (YWHAZ) to repress expression of E-cadherin by preventing dimerization of 14-3-3ζ and inhibiting migration of non-small cell lung cancer cells.

    “Recently, it was found that NLK interacts with 14-3-3ζ (also known as YWHAZ) to repress the expression of E-cadherin by preventing dimerization of 14-3-3ζ and inhibiting the migration of non-small cell lung cancer cells [24].”

    From Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies (2020) · cites this paper as [24]

    The Results report that NLK inhibits 14-3-3ζ dimerization and restores E-cadherin expression repressed by 14-3-3ζ in A549 cells—the opposite of the claim that NLK represses E-cadherin. The Abstract and Introduction likewise say NLK restores E-cadherin and inhibits migration. Although the Discussion's concluding sentence says “represses,” it conflicts with the paper's reported findings. (LLM, conf=0.90)

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Research works printed but not linked: 26

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Sorted by citations

Authors
Chen, J., Lin, Q., Ni, T., Zhao, J., Lin, F., Lu, X., Lv, Y., Ren, S., Liu, Z., Zhang, T., He, S., Shen, D., & Mao, W.
Affiliations
  • Xuzhou Medical College (CN)
  • Nantong University (CN)
Corresponding author
  • Shen, Dong
  • Mao, Weidong
ORCID
Venue
Oncology Reports
Publisher
Spandidos Publications
Published
2020-03-20
Volume
43
Issue
6
Pages
1845-1852
ISSN
  • 1021-335X (ISSN-L)
  • 1791-2431
DOI
10.3892/or.2020.7557
PMC
PMC7160556
OpenAlex
W3011672226
Cited by
4
References
0
Citations by year
2024: 1 · 2023: 1 · 2020: 2
FWCI
0.24
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Oncology Reports (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Wuxi Health and Family Planning Commission
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 14-3-3 protein interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
Nemo-like kinase, 14-3-3ζ, E-cadherin, epithelial-mesenchymal transition, non-small cell lung cancer, protein-protein interaction, tumor suppressor, cell migration, A549 cells
MeSH terms
A549 Cells, Carcinoma, Non-Small-Cell Lung, Cell Movement, Humans, Lung Neoplasms, Antigens, CD, Cadherins, Gene Expression Regulation, Neoplastic, Protein Serine-Threonine Kinases, Cell Line, Tumor, 14-3-3 Proteins, Cell Proliferation, Protein Stability, HEK293 Cells, Epithelial-Mesenchymal Transition

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