Role of sodium/iodide symporter overexpression in inhibiting thyroid cancer cell invasion and stem cell maintenance by inhibiting the β-catenin/LEF-1 pathway
Background: 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 thyro...
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Elsevier
2024-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024038714 |
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| author | Nan-Fang Luo Jia-Li Li Juan Lv Fu-Kun Chen Ya-Nan Li Ming Tang Peng-Jie Liu |
| author_facet | Nan-Fang Luo Jia-Li Li Juan Lv Fu-Kun Chen Ya-Nan Li Ming Tang Peng-Jie Liu |
| author_sort | Nan-Fang Luo |
| collection | DOAJ |
| description | Background: 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. Methods: 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.). Results: 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. Conclusion: 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. |
| first_indexed | 2024-04-24T13:49:39Z |
| format | Article |
| id | doaj.art-bb0b1912aa6c4551a1a0997f72f681ae |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T13:49:39Z |
| publishDate | 2024-03-01 |
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| series | Heliyon |
| spelling | doaj.art-bb0b1912aa6c4551a1a0997f72f681ae2024-04-04T05:06:07ZengElsevierHeliyon2405-84402024-03-01106e27840Role of sodium/iodide symporter overexpression in inhibiting thyroid cancer cell invasion and stem cell maintenance by inhibiting the β-catenin/LEF-1 pathwayNan-Fang Luo0Jia-Li Li1Juan Lv2Fu-Kun Chen3Ya-Nan Li4Ming Tang5Peng-Jie Liu6Department of Cardiac Function, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, ChinaDepartment of Nuclear Medicine, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, ChinaDepartment of Nuclear Medicine, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, ChinaDepartment of Nuclear Medicine, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, ChinaDepartment of Nuclear Medicine, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, ChinaDepartment of Pathology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, China; Corresponding author. Department of Pathology The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No.157 of JinBi Road, Xishan District, Kunming 650032, China.Department of Nuclear Medicine, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, China; Corresponding author. Department of Nuclear Medicine, The Cancer Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, No. 519 of Kunzhou Road, Xishan District, Kunming 650118, China.Background: 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. Methods: 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.). Results: 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. Conclusion: 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.http://www.sciencedirect.com/science/article/pii/S2405844024038714β-CateninLEF-1Papillary thyroid carcinomaSodium iodide symporter (NIS) |
| spellingShingle | Nan-Fang Luo Jia-Li Li Juan Lv Fu-Kun Chen Ya-Nan Li Ming Tang Peng-Jie Liu Role of sodium/iodide symporter overexpression in inhibiting thyroid cancer cell invasion and stem cell maintenance by inhibiting the β-catenin/LEF-1 pathway Heliyon β-Catenin LEF-1 Papillary thyroid carcinoma Sodium iodide symporter (NIS) |
| title | Role of sodium/iodide symporter overexpression in inhibiting thyroid cancer cell invasion and stem cell maintenance by inhibiting the β-catenin/LEF-1 pathway |
| title_full | Role of sodium/iodide symporter overexpression in inhibiting thyroid cancer cell invasion and stem cell maintenance by inhibiting the β-catenin/LEF-1 pathway |
| title_fullStr | Role of sodium/iodide symporter overexpression in inhibiting thyroid cancer cell invasion and stem cell maintenance by inhibiting the β-catenin/LEF-1 pathway |
| title_full_unstemmed | Role of sodium/iodide symporter overexpression in inhibiting thyroid cancer cell invasion and stem cell maintenance by inhibiting the β-catenin/LEF-1 pathway |
| title_short | Role of sodium/iodide symporter overexpression in inhibiting thyroid cancer cell invasion and stem cell maintenance by inhibiting the β-catenin/LEF-1 pathway |
| title_sort | role of sodium iodide symporter overexpression in inhibiting thyroid cancer cell invasion and stem cell maintenance by inhibiting the β catenin lef 1 pathway |
| topic | β-Catenin LEF-1 Papillary thyroid carcinoma Sodium iodide symporter (NIS) |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024038714 |
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