TSHR Promotes Proliferation and Invasion of Papillary Thyroid Carcinoma By Regulating NF-κB Signal Pathway

Abstract Purpose: To investigate the significance of TSHR and NF-κB P65 expression difference in thyroid papillary carcinoma, and to explore how TSHR affects the biological behavior of PTC cells by regulating NF signaling pathway .Methods: A total of 87 patients with thyroid papillary carcinoma were collected to investigate the expression of TSHR and NF-κB P65 in PTC by IHC. Tpc-1 cells overexpressing TSHR were constructed and their effects on cell biological behavior were observed by cell counting and Transwell assays. Subsequently, the expression and subcellular localization of key proteins in NF-κB signaling pathway were investigated by western blot and immunofluorescence.Results: 1. The expression of TSHR in PTC was significantly higher than normal tissues and was only negatively correlated with lymph node metastasis. The NF-κB p65 was also highly expressed in cancer tissues, and was positively associated with tumor size, membrane invasion and lymph node metastasis, and unrelated to gender and age. There was a lightly positive correlation between TSHR and NF-κB p65 expression.2. The proliferation and invasion ability of TPC-1 cells overexpressing TSHR was suppressed. the expression of P65 showed no change with TSHR in TPC-1 cells, but p-p65 and p-IκB was significantly increased with TSHR overexpressing. Finally, TSHR promoted the p65 to enter into nucleus.Conclusion: Our study uncovered TSHR may inhibited the proliferation and invasion ability of PTC by NF-κB signaling pathways. Furthermore, we revealed that TSHR may acted as a functional protein in tumor cells without the stimulation of TSH.