Inhibiting β-catenin expression promotes efficiency of radioiodine treatment in aggressive follicular thyroid cancer cells probably through mediating NIS localization

Lan,Ling; Basourakos,Spyros; Cui,Dai; Zuo,Xuemei; Deng,Wei; Huo,Lili; Chen,Linghai; Zhang,Guoying; Deng,Lili; Shi,Bingyin; Luo,Yong

doi:10.3892/or.2016.5228

Inhibiting β-catenin expression promotes efficiency of radioiodine treatment in aggressive follicular thyroid cancer cells probably through mediating NIS localization

Authors:
- Ling Lan
- Spyros Basourakos
- Dai Cui
- Xuemei Zuo
- Wei Deng
- Lili Huo
- Linghai Chen
- Guoying Zhang
- Lili Deng
- Bingyin Shi
- Yong Luo
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Affiliations: Department of Endocrinology, Beijing Jishuitan Hospital, Beijing 100035, P.R. China, Department of Genitourinary, Cancer Medicine, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA, Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Endocrinology, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: November 7, 2016 https://doi.org/10.3892/or.2016.5228
Pages: 426-434

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Abstract

The present study investigated whether the efficacy of radioiodine therapy towards aggressive thyroid cancer cells was affected by β-catenin activity and associated with sodium/iodine symporter (NIS) localization. Human thyroid cancer cell line follicular thyroid carcinoma (FTC) 133 was endowed with aggressiveness by HIF-1α or β-catenin overexpression. The protein amount and subcellular localization of NIS, and the radioiodine uptake capacity were detected in the cells, as well as in cells subsequently undergoing β-catenin knockdown. Xenograft experiments were conducted to compare the tumor growth ability and responsiveness to radioactive treatment among HIF-1α and β-catenin overexpressing FTC cells, respectively with or without β-catenin knockdown. β-catenin increased upon HIF-1α overexpression, but not vice versa. This signal axis would prompt metastatic propensity in FTC cells, and translocate NIS from cytomembrane to cytoplasm. Consistently the radioiodine uptake capacity in the cells decreased obviously. Knockdown of β-catenin reversed all these changes. Furthermore, the xenograft experiments showed that radioiodine treatment could thoroughly suppress tumor growth ability of aggressive FTC cells only if the HIF-1α-induced β-catenin activation was disrupted by β-catenin knockdown. β-catenin nuclear translocation in tumor cells was accompanied by abnormal subcellular localization of NIS. Moreover, we found that only after inhibiting β-catenin expression, can the radioiodine treatment promote apoptosis other than repress proliferation and survival in xenograft tumor cells. In conclusion, aggressive FTC cells overexpressing HIF-1α will be fully cracked down by radioiodine therapy once β-catenin expression is inhibited, and regulated localization of NIS may account for underlying mechanisms.

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