TESC promotes differentiated thyroid cancer development by activating ERK and weakening NIS and radioiodine uptake

Abstract

Most differentiated thyroid cancer (DTC) patients have a good prognosis after surgery, but radioiodine refractory differentiated thyroid cancer (RAIR-DTC) patients have a signi cantly reduced ve-year survival rate (< 60%) and a signi cantly increased recurrence rate (> 30%). This study aimed to clarify the tescalcin (TESC) role in promoting the malignant PTC progression and providing a potential target for RAIR-DTC treatment. MethodsWe analyzed TESC expression and clinicopathological characteristics using the Cancer Genome Atlas (TCGA) and performed qRT-PCR on tissue samples. TPC-1 and IHH4 proliferation, migration, and invasion were detected after transfection with TESC-RNAi. Using Western blot (WB), several EMT-related indicators were detected. Moreover, iodine uptake of TPC-1 and IHH4 after transfection with TESC-RNAi was detected. Finally, NIS, ERK1/2, and p-ERK1/2 levels were determined by WB. ResultsTESC was signi cantly upregulated in DTC tissues and positively correlated with BRAF V600E mutation based on data analysis from TCGA and our center. Reduced expression of TESC in both IHH-4 (BRAF V600E mutation) and TPC-1 (BRAF V600E wild type) cells signi cantly inhibited cell proliferation, migration, and invasion. It downregulated the EMT pathway markers Vimentin and N-cadherin, and increased E-cadherin. Moreover, TESC knockdown signi cantly inhibited ERK1/2 phosphorylation and decreased NIS expression in DTC cells, with a remarkably increased iodine uptake rate. ConclusionsTESC was highly expressed in DTC tissues and may have promoted metastasis through EMT and induced iodine resistance by downregulating NIS in DTC cells.