Study on the mechanism of TP53 degradation by SFN ubiquitination affecting locally advanced TC progression.

AIM: Revealing the molecular mechanism of metastasis of advanced thyroid cancer and transforming it into neoadjuvant targeted therapy, to get a great potential to reduce operative mortality and improve clinical prognosis in locally advanced Thyroid Cancer (TC) patients.

METHODS

Serological tests were conducted to detect the expression level of natural TF-Ab and the sialacidification level of Thomson friedenreich antibody (TF-Ab) in the population; Analysis of downstream acting proteins after exposure to TF-Ag by IP binding mass spectrometry. Clinical histological immunohistochemistry confirmed the expression of the target protein in locally advanced TC tissues. In vitro and in vivo experiments verified the influence of target protein expression regulation on the biological functions of TC cells and tumor progression.

RESULTS

The expression of natural TF-Ab in tumor patients is lower than that in healthy people, while there was no significant difference in the level of sialacidification among antibodies; IP combined with mass spectrometry showed that SFN was a stable and highly expressed molecular interaction protein after exposure to TF-Ag. Clinical histology verified that SFN was significantly higher expressed in locally advanced TC tissues than in inert TC tissues (T1 stage). Cell biology experiments have demonstrated that SFN expression regulation can significantly affect the biological function of TC cells and change the differentiation ratio of CSCs. Intervention of SFN expression in vivo tumor formation experiments in nude mice can significantly inhibit tumor progression.

CONCLUSION

The effect of TP53 degradation by SFN ubiquitination on the differentiation of CSCs is a potential molecular mechanism for the widespread metastasis of locally advanced TC.