Adaptor protein LNK promotes anaplastic thyroid carcinoma cell growth via 14-3-3 ϵ/γbinding

Zhao Ming Zhong, Xue Chen, Xiao Qi, Xue Min Wang, Chun Yan Li, Ru Jia Qin, Shi Qi Wang, Jin Liang, Mu Sheng Zeng, Chuan Zheng Sun

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Abstract

Background: Rapid progression contributes to treatment failure in anaplastic thyroid carcinoma (ATC) patients. In a preliminary study, we demonstrated that some hematopoietic factors may be involved in the progression of ATC. The adaptor protein LNK, which is a negative regulator of hematopoietic cytokine signalling, has been studied extensively in malignant hematopoietic cells. However, there are few studies on LNK in solid tumours. Methods: Real-time PCR, immunohistochemistry (IHC) and western blot analysis of LNK were performed on ATC cells, differentiated thyroid cancer (DTC) cells and normal thyroid cells. In vitro assays (including pull-down, liquid chromatography-mass spectrometry (LC-MS), co-IP, MTT and colony formation) were performed to validate the effect of LNK on ATC progression and elucidate the molecular mechanisms. Results: Compared with DTC cells and normal thyroid cells, ATC cells exhibit overexpression of LNK. In addition, LNK overexpression results in increased proliferation of ATC cells. Conversely, LNK knockdown significantly suppresses ATC cell proliferation. LC-MS identified the 14-3-3 ϵ/γprotein as a LNK binding partner. Finally, the results indicate that LNK overexpression significantly enhances the anti-apoptotic ability of ATC cells via the Akt-NFκB-Bcl-2/Bcl-xL pathway and that the oncogenic effect of LNK largely depends on 14-3-3 ϵ/γbinding. Conclusions: The present study elucidated the important role of LNK in the growth of ATC opposite to its behaviour in the hematopoietic system and indicates that LNK is a potential target for the treatment of ATC.

Original languageEnglish (US)
Article number11
JournalCancer Cell International
Volume20
Issue number1
DOIs
Publication statusPublished - Jan 9 2020

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Keywords

  • 14-3-3 ϵ/γ
  • Adaptor protein
  • Anaplastic thyroid carcinoma
  • Cell growth
  • LNK

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

Cite this

Zhong, Z. M., Chen, X., Qi, X., Wang, X. M., Li, C. Y., Qin, R. J., ... Sun, C. Z. (2020). Adaptor protein LNK promotes anaplastic thyroid carcinoma cell growth via 14-3-3 ϵ/γbinding. Cancer Cell International, 20(1), [11]. https://doi.org/10.1186/s12935-019-1090-9