Journal
CANCER CELL INTERNATIONAL
Volume 20, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12935-019-1090-9
Keywords
Adaptor protein; Anaplastic thyroid carcinoma; Cell growth; LNK; 14-3-3 epsilon/gamma
Categories
Funding
- National Natural Science Founda-tion of China [81560470, 81773127, 81960543]
- Special Foundation of Young and Middle-Aged Academic Leaders Reserve Talent in Yunnan Province [2015HB086]
- Special Funds for High-Level Medical Leaders in Yunnan Province [L-2017025]
- Yunnan Province Basic Research Program [2018FE001-058/246]
Ask authors/readers for more resources
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 epsilon/gamma protein as a LNK binding partner. Finally, the results indicate that LNK overexpression significantly enhances the anti-apoptotic ability of ATC cells via the Akt-NF kappa B-Bcl-2/Bcl-xL pathway and that the oncogenic effect of LNK largely depends on 14-3-3 epsilon/gamma binding. 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available