Abstract
BackgroundRapid 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.MethodsReal-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.ResultsCompared 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/γ 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-NFκB-Bcl-2/Bcl-xL pathway and that the oncogenic effect of LNK largely depends on 14-3-3 ε/γ binding.ConclusionsThe 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.
Highlights
Rapid progression contributes to treatment failure in anaplastic thyroid carcinoma (ATC) patients
Our data indicated that the mRNA and protein expression levels of LNK were significantly increased in the ATC cells compared with those in the differentiated thyroid cancer (DTC) and normal thyroid cells
The results showed that LNK overexpression could cause an elevated expression of 14-3-3 proteins accompanied by increased levels of phosphorylated Akt, and enhance the expression of the anti-apoptotic proteins B cell lymphoma-2 (Bcl-2), Bcl-xL and nuclear factor-kappa B (NFκB) and downregulate the activation of the pro-apoptotic protein caspase-7/9
Summary
Rapid progression contributes to treatment failure in anaplastic thyroid carcinoma (ATC) patients. We demonstrated that some hematopoietic factors may be involved in the progression of ATC. Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers in humans. A. Previously, we found that increased white blood cell and platelet counts are negatively correlated with the prognosis of ATC patients [4]. Zhong et al Cancer Cell Int (2020) 20:11 that the hematopoietic factors interleukin-11 and colonystimulating factor-1 significantly increased the invasive and migratory abilities of ATC cells [4, 5]. We speculated that some genes that regulate hematopoietic factors are involved in the progression of ATC. Recent research has shown that functional deletion mutations in LNK, an important hematopoietic suppressor gene, lead to a > 10-fold increase in hematopoietic stem cell numbers owing to superior hematopoietic stem cell self-renewal [6] and gives rise to myeloproliferative neoplasms characterized by platelet and leukocyte overproduction [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
