Luo Nan-Fang, Li Jia-Li, Lv Juan, Chen Fu-Kun, Li Ya-Nan, Tang Ming, Liu Peng-Jie
Department of Cardiac Function, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, China.
Department of Nuclear Medicine, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, China.
Heliyon. 2024 Mar 14;10(6):e27840. doi: 10.1016/j.heliyon.2024.e27840. eCollection 2024 Mar 30.
In thyroid cancers, a reduction in the expression of the sodium/iodide symporter (NIS) is observed concomitant with a diminution in cancer cell differentiation. The β-catenin/LEF-1 pathway emerges as a crucial regulatory pathway influencing the functional expression of NIS in human thyroid cancer cells. Further research is required to comprehensively elucidate the role of NIS overexpression in impeding the progression of thyroid cancer cells.
Human papillary thyroid carcinoma (PTC) cell lines, specifically PTC-1 and KTC-1, were subjected to Scratch and Transwell assays, colony formation, and tumor sphere formation tests to investigate invasion and migration, focusing on the impact of NIS overexpression. The assessment involved the use of western blot to analyze the expression levels of β-catenin, NIS, CD133, SRY-related HMG box2 (Sox2), lymphoid enhancer-binding factor 1 (LEF-1), NANOG, octamer-binding transcription factor 4 (Oct4), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), and epithelial cellular adhesion molecule (EpCAM). Statistical analysis was conducted using SPSS version 20.0, and the graphs were developed using GraphPad Prism 7 (GraphPad Software, Inc.).
Our observations revealed that Nthy-ori-3-1 cell lines exhibited notably higher average expression levels of NIS, yet significantly lower levels of LEF-1 and β-catenin compared to PTC-1 and KTC-1 cell lines. Furthermore, the overexpression of β-catenin resulted in reduced binding of LEF-1 to NIF promotion but concurrently increased the expression of NIS. The downregulation of NIS markedly enhanced the expression of ALDH1A1, CD133, OCT4, Nanog, SOX2, and EpCam-all of which are targets within the Wnt/β-catenin signaling pathway. Conversely, the upregulation of NIS suppressed the expression of these proteins. Moreover, cells treated with β-catenin activators demonstrated an increased capability to form more spheroids and displayed heightened aggressiveness. Conversely, the NIS overexpression (OE) group exhibited suppressed abilities in invasion and colony formation.
Thyroid cancer cells exhibit diminished expression of NIS, and the invasion and maintenance of stem cells in thyroid cancer cells were hindered by NIS OE through the inhibition of the β-catenin/LEF-1 pathway. Further research is warranted to comprehensively assess this outcome, which holds promise as a potential targeted treatment for thyroid cancer.
在甲状腺癌中，观察到钠/碘同向转运体（NIS）的表达降低，同时癌细胞分化也减少。β-连环蛋白/淋巴样增强因子1（LEF-1）信号通路是影响人甲状腺癌细胞中NIS功能表达的关键调节通路。需要进一步研究以全面阐明NIS过表达在阻碍甲状腺癌细胞进展中的作用。
对人甲状腺乳头状癌（PTC）细胞系，特别是PTC-1和KTC-1，进行划痕试验、Transwell试验、集落形成试验和肿瘤球形成试验，以研究侵袭和迁移情况，重点关注NIS过表达的影响。评估过程中使用蛋白质印迹法分析β-连环蛋白、NIS、CD133、SRY相关高迁移率族盒蛋白2（Sox2）、淋巴样增强因子1（LEF-1）、NANOG、八聚体结合转录因子4（Oct4）、醛脱氢酶1家族成员A1（ALDH1A1）和上皮细胞黏附分子（EpCAM）的表达水平。使用SPSS 20.0版进行统计分析，使用GraphPad Prism 7（GraphPad软件公司）绘制图表。
我们的观察结果显示，与PTC-1和KTC-1细胞系相比，Nthy-ori-3-1细胞系的NIS平均表达水平显著更高，但LEF-1和β-连环蛋白水平显著更低。此外，β-连环蛋白的过表达导致LEF-1与NIF启动子的结合减少，但同时NIS的表达增加。NIS的下调显著增强了ALDH1A1、CD133、OCT4、Nanog、SOX2和EpCam的表达，这些都是Wnt/β-连环蛋白信号通路中的靶点。相反，NIS的上调抑制了这些蛋白的表达。此外，用β-连环蛋白激活剂处理的细胞形成更多球体的能力增强，并且表现出更高的侵袭性。相反，NIS过表达（OE）组在侵袭和集落形成方面的能力受到抑制。
甲状腺癌细胞中NIS表达降低，NIS过表达通过抑制β-连环蛋白/LEF-1信号通路阻碍甲状腺癌细胞中干细胞的侵袭和维持。有必要进行进一步研究以全面评估这一结果，这有望成为甲状腺癌的一种潜在靶向治疗方法。
