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05.04.2023 | Original Article

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

verfasst von: Yawen Guo, Yefeng Cai, Fahuan Song, Lei Zhu, Yiqun Hu, Yunye Liu, Wenli Ma, Jingyan Ge, Qian Zeng, Lingling Ding, Lebao Li, Guowan Zheng, Minghua Ge

Erschienen in: Endocrine | Ausgabe 3/2023

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Abstract

Purpose

Most differentiated thyroid cancer (DTC) patients have a good prognosis after surgery, but radioiodine refractory differentiated thyroid cancer (RAIR-DTC) patients have a significantly reduced 5-year survival rate (<60%) and a significantly 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.

Methods

We analyzed TESC expression and clinicopathological characteristics using the Cancer Genome Atlas (TCGA) and performed qRT-PCR on tissue samples. TPC-1 and IHH-4 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 IHH-4 after transfection with TESC-RNAi was detected. Finally, NIS, ERK1/2, and p-ERK1/2 levels were determined by WB.

Results

TESC was significantly 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 significantly inhibited cell proliferation, migration, and invasion. It downregulated the EMT pathway markers Vimentin and N-cadherin, and increased E- cadherin. Moreover, TESC knockdown significantly inhibited ERK1/2 phosphorylation and decreased NIS expression in DTC cells, with a remarkably increased iodine uptake rate.

Conclusions

TESC was highly expressed in DTC tissues and may have promoted metastasis through EMT and induced iodine resistance by downregulating NIS in DTC cells.

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Titel: TESC promotes differentiated thyroid cancer development by activating ERK and weakening NIS and radioiodine uptake
verfasst von: Yawen Guo
Yefeng Cai
Fahuan Song
Lei Zhu
Yiqun Hu
Yunye Liu
Wenli Ma
Jingyan Ge
Qian Zeng
Lingling Ding
Lebao Li
Guowan Zheng
Minghua Ge
Publikationsdatum: 05.04.2023
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 3/2023
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-023-03350-6

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