ATRA increases iodine uptake and inhibits the proliferation and invasiveness of human anaplastic thyroid carcinoma SW1736 cells: Involvement of β‑catenin phosphorylation inhibition

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

doi:10.3892/ol.2017.7225

ATRA increases iodine uptake and inhibits the proliferation and invasiveness of human anaplastic thyroid carcinoma SW1736 cells: Involvement of β‑catenin phosphorylation inhibition

Authors:
- Ling Lan
- Spyros Basourakos
- Dai Cui
- Xuemei Zuo
- Wei Deng
- Lili Huo
- Hailing Chen
- Guoying Zhang
- Lili Deng
- Bingyin Shi
- Yong Luo
View Affiliations

Affiliations: Department of Endocrinology, Beijing Jishuitan Hospital, Beijing 100035, P.R. China, Department of Genitourinary, Cancer Medicine, MD Anderson Cancer Center, 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, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: October 19, 2017 https://doi.org/10.3892/ol.2017.7225
Pages: 7733-7738
Copyright: © Lan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

All-trans-retinoic acid (ATRA) can enhance iodine uptake capability of thyroid tumors, but the mechanisms remain poorly understood. The aim of the present study was to investigate the effects of ATRA on isotope susceptibility, proliferation and invasion of anaplastic thyroid carcinoma (ATC) and potential mechanisms. SW1736 cells were treated with 1 µmol/l ATRA or 1% ethanol for 5 days. A cell line stably expressing β‑catenin‑shRNA was established. An iodine uptake assay was performed using 125I. Proliferation and invasiveness were tested using MTT and Transwell assays, respectively. Western blotting was used to assess the expression of β‑catenin, glycogen synthase kinase‑3β (GSK‑3β), sodium/iodine symporter (NIS) and proteins involved in epithelial‑mesenchymal transition. Cells pretreated with ATRA were injected subcutaneously into SCID mice. Mice were intraperitoneally injected with 131I once on the first day of treatment, and tumor growth was then assessed. After 35 days of 131I treatment, ATRA‑pretreated tumor volume and weight were decreased compared with the 131I alone group (163.32±19.57 vs. 332.06±21.37 mm3; 0.35±0.14 vs. 0.67±0.23 g, both P<0.05). Similar results were observed in the β‑catenin shRNA‑pretreated tumors. ATRA also increased the uptake of iodine by SW1736 cells (P<0.01), and similar results were observed in β‑catenin shRNA cells. ATRA treatment decreased the cell proliferation and invasion compared with control cells (all P<0.05), similar to β‑catenin shRNA. ATRA treatment decreased the expression of phosphorylated (p‑)β‑catenin, p‑GSK‑3β, vimentin, and fibronectin, and increased the expression of NIS and E‑cadherin, compared with the control. ATRA increased the iodine uptake and inhibited the proliferation and invasion of SW1736 cells, involving β‑catenin phosphorylation. In conclusion, ATRA could be used to improve the isotope sensitivity of ATC.

View Figures

View References

1	Kojic KL, Kojic SL and Wiseman SM: Differentiated thyroid cancers: A comprehensive review of novel targeted therapies. Expert Rev Anticancer Ther. 12:345–357. 2012. View Article : Google Scholar : PubMed/NCBI
2	Smallridge RC, Ain KB, Asa SL, Bible KC, Brierley JD, Burman KD, Kebebew E, Lee NY, Nikiforov YE, Rosenthal MS, et al: American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid. 22:1104–1139. 2012. View Article : Google Scholar : PubMed/NCBI
3	Glaser SM, Mandish SF, Gill BS, Balasubramani GK, Clump DA and Beriwal S: Anaplastic thyroid cancer: Prognostic factors, patterns of care, and overall survival. Head Neck. 38 Suppl 1:E2083–E2090. 2016. View Article : Google Scholar : PubMed/NCBI
4	Schenk T, Stengel S and Zelent A: Unlocking the potential of retinoic acid in anticancer therapy. Br J Cancer. 111:2039–2045. 2014. View Article : Google Scholar : PubMed/NCBI
5	Gutierrez-Mazariegos J, Schubert M and Laudet V: Evolution of retinoic acid receptors and retinoic acid signaling. Subcell Biochem. 70:55–73. 2014. View Article : Google Scholar : PubMed/NCBI
6	Leelawat K, Ohuchida K, Mizumoto K, Mahidol C and Tanaka M: All-trans retinoic acid inhibits the cell proliferation but enhances the cell invasion through up-regulation of c-met in pancreatic cancer cells. Cancer Lett. 224:303–310. 2005. View Article : Google Scholar : PubMed/NCBI
7	Liu SM, Chen W and Wang J: Distinguishing between cancer cell differentiation and resistance induced by all-trans retinoic acid using transcriptional profiles and functional pathway analysis. Sci Rep. 4:55772014. View Article : Google Scholar : PubMed/NCBI
8	Tari AM, Lim SJ, Hung MC, Esteva FJ and Lopez-Berestein G: Her2/neu induces all-trans retinoic acid (ATRA) resistance in breast cancer cells. Oncogene. 21:5224–5232. 2002. View Article : Google Scholar : PubMed/NCBI
9	Zhang M, Guo R, Xu H, Zhang M and Li B: Retinoic acid and tributyrin induce in-vitro radioiodine uptake and inhibition of cell proliferation in a poorly differentiated follicular thyroid carcinoma. Nucl Med Commun. 32:605–610. 2011. View Article : Google Scholar : PubMed/NCBI
10	Muhlbauer M, da Silva AC, Marassi MP, Lourenço AL, Ferreira AC and de Carvalho DP: Retinoic acid modulation of thyroid dual oxidase activity in rats and its impact on thyroid iodine organification. J Endocrinol. 205:271–277. 2010. View Article : Google Scholar : PubMed/NCBI
11	Tang M, Hou YL, Kang QQ, Chen XY, Duan LQ, Shu J, Li SL, Hu XL and Peng ZP: All-trans-retinoic acid promotes iodine uptake via up-regulating the sodium iodide symporter in medullary thyroid cancer stem cells. Asian Pac J Cancer Prev. 15:1859–1862. 2014. View Article : Google Scholar : PubMed/NCBI
12	Dohan O, De la Vieja A, Paroder V, Riedel C, Artani M, Reed M, Ginter CS and Carrasco N: The sodium/iodide symporter (NIS): Characterization, regulation, and medical significance. Endocr Rev. 24:48–77. 2003. View Article : Google Scholar : PubMed/NCBI
13	Furuya F, Shimura H, Suzuki H, Taki K, Ohta K, Haraguchi K, Onaya T, Endo T and Kobayashi T: Histone deacetylase inhibitors restore radioiodide uptake and retention in poorly differentiated and anaplastic thyroid cancer cells by expression of the sodium/iodide symporter thyroperoxidase and thyroglobulin. Endocrinology. 145:2865–2875. 2004. View Article : Google Scholar : PubMed/NCBI
14	Sastre-Perona A and Santisteban P: Wnt-independent role of β-catenin in thyroid cell proliferation and differentiation. Mol Endocrinol. 28:681–695. 2014. View Article : Google Scholar : PubMed/NCBI
15	Lan L, Deng W, Chen HL, Huo L, Deng L, Zhang G and Luo Y: Nuclear translocation of β-catenin represses membrane localization of NIS in human thyroid cancer cells. Zhonghua Yi Xue Za Zhi. 96:891–896. 2016.PubMed/NCBI
16	Haberkorn U, Altmann A, Jiang S, Morr I, Mahmut M and Eisenhut M: Iodide uptake in human anaplastic thyroid carcinoma cells after transfer of the human thyroid peroxidase gene. Eur J Nucl Med. 28:633–638. 2001. View Article : Google Scholar : PubMed/NCBI
17	Jiang Y, Zhao J, Wu C, Luo Y and He D: Construction and identification of shRNA eukaryotic vector targeting human β-catenin. Acad J Second Milit Med Uni. 30:965–967. 2009. View Article : Google Scholar
18	Nakamoto Y, Saga T, Misaki T, Kobayashi H, Sato N, Ishimori T, Kosugi S, Sakahara H and Konishi J: Establishment and characterization of a breast cancer cell line expressing Na+/I-symporters for radioiodide concentrator gene therapy. J Nucl Med. 41:1898–1904. 2000.PubMed/NCBI
19	Sastre-Perona A and Santisteban P: Role of the wnt pathway in thyroid cancer. Front Endocrinol (Lausanne). 3:312012.PubMed/NCBI
20	Ryan J, Curran CE, Hennessy E, Newell J, Morris JC, Kerin MJ and Dwyer RM: The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue. PLoS One. 6:e160232011. View Article : Google Scholar : PubMed/NCBI
21	Cheong SJ, Jang D, Jeong HJ, Lim ST, Sohn MH, Katzenellenbogen JA and Kim DW: Reduction of stimulated sodium iodide symporter expression by estrogen receptor ligands in breast cancer cells. Nucl Med Biol. 38:287–294. 2011. View Article : Google Scholar : PubMed/NCBI
22	Lee SJ, Kim SH, Kang JG, Kim CS, Ihm SH, Choi MG and Yoo HJ: Effects of all-trans retinoic acid on sodium/iodide symporter and CCAAT/enhancer-binding protein-homologous protein under condition of endoplasmic reticulum stress in FRTL5 thyroid cells. Horm Metab Res. 43:331–336. 2011. View Article : Google Scholar : PubMed/NCBI
23	Beyer S, Lakshmanan A, Liu YY, Zhang X, Wapnir I, Smolenski A and Jhiang S: KT5823 differentially modulates sodium iodide symporter expression, activity, and glycosylation between thyroid and breast cancer cells. Endocrinology. 152:782–792. 2011. View Article : Google Scholar : PubMed/NCBI
24	Willhauck MJ, Kane ODJ, Wunderlich N, Göke B and Spitzweg C: Stimulation of retinoic acid-induced functional sodium iodide symporter (NIS) expression and cytotoxicity of ¹³¹I by carbamazepine in breast cancer cells. Breast Cancer Res Treat. 125:377–386. 2011. View Article : Google Scholar : PubMed/NCBI
25	Kang HJ, Youn YK, Hong MK and Kim LS: Antiproliferation and redifferentiation in thyroid cancer cell lines by polyphenol phytochemicals. J Korean Med Sci. 26:893–899. 2011. View Article : Google Scholar : PubMed/NCBI
26	Malehmir M, Haghpanah V, Larijani B, Ahmadian S, Alimoghaddam K, Heshmat R, Ghavamzadeh A, Adabi K and Ghaffari SH: Multifaceted suppression of aggressive behavior of thyroid carcinoma by all-trans retinoic acid induced re-differentiation. Mol Cell Endocrinol. 348:260–269. 2012.PubMed/NCBI
27	Lan L, Cui D, Luo Y, Shi BY, Deng LL, Zhang GY and Wang H: Inhibitory effects of retinoic acid on invasiveness of human thyroid carcinoma cell lines in vitro. J Endocrinol Invest. 32:731–738. 2009. View Article : Google Scholar : PubMed/NCBI
28	Dutta A, Sen T and Chatterjee A: All-trans retinoic acid (ATRA) downregulates MMP-9 by modulating its regulatory molecules. Cell Adh Migr. 4:409–418. 2010. View Article : Google Scholar : PubMed/NCBI
29	Vasko V, Espinosa AV, Scouten W, He H, Auer H, Liyanarachchi S, Larin A, Savchenko V, Francis GL, de la Chapelle A, et al: Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion. Proc Natl Acad Sci USA. 104:pp. 2803–2808. 2007, View Article : Google Scholar : PubMed/NCBI
30	Jang GB, Kim JY, Cho SD, Park KS, Jung JY, Lee HY, Hong IS and Nam JS: Blockade of Wnt/β-catenin signaling suppresses breast cancer metastasis by inhibiting CSC-like phenotype. Sci Rep. 5:124652015. View Article : Google Scholar : PubMed/NCBI
31	Mao J, Fan S, Ma W, Fan P, Wang B, Zhang J, Wang H, Tang B, Zhang Q, Yu X, et al: Roles of Wnt/β-catenin signaling in the gastric cancer stem cells proliferation and salinomycin treatment. Cell Death Dis. 5:e10392014. View Article : Google Scholar : PubMed/NCBI