NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT
Ru-Tian Hao, Chen Zheng, Chen-Yong Wu, Er-Jie Xia, Xiao-Fen Zhou, Rui-Da Quan, Xiao-Hua ZhangDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou, Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaAbstract: Papillary thyroid cancer (PTC) is the...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-04-01
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| Series: | Cancer Management and Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/nectin4-promotes-papillary-thyroid-cancer-cell-proliferation-migration-peer-reviewed-article-CMAR |
| _version_ | 1828350236392685568 |
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| author | Hao RT Zheng C Wu CY Xia EJ Zhou XF Quan RD Zhang XH |
| author_facet | Hao RT Zheng C Wu CY Xia EJ Zhou XF Quan RD Zhang XH |
| author_sort | Hao RT |
| collection | DOAJ |
| description | Ru-Tian Hao, Chen Zheng, Chen-Yong Wu, Er-Jie Xia, Xiao-Fen Zhou, Rui-Da Quan, Xiao-Hua ZhangDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou, Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaAbstract: Papillary thyroid cancer (PTC) is the most frequent type of malignant thyroid cancer, but its molecular mechanisms remain unknown. To better understand the tumorigenesis and progression of PTC, we conducted a comprehensive analysis of the whole-transcriptome resequencing of paired PTC and normal thyroid tissues. Nectin cell adhesion molecule 4 (NECTIN4) was significantly overexpressed in thyroid carcinoma compared with that in matched normal tissue. We also assessed the relation between the expression level of NECTIN4 and the clinicopathological features of PTC in The Cancer Genome Atlas database, and results showed that upregulated NECTIN4 is associated with lymph node metastasis (P<0.001) and tumor size (P=0.017). The biological function of NECTIN4 was also investigated by using the PTC cell lines TPC-1 and KTC-1. In vitro experiments demonstrated that NECTIN4 downregulation significantly inhibits the colony formation, proliferation, migration, and invasion of PTC cell lines. NECTIN4 could modulate the expression of epithelial–mesenchymal transition-related proteins via the PI3K/AKT pathway, and SC79, an AKT phosphorylation activator, could reverse the si-RNA knockdown effect. In addition, after the use of AKT inhibitors (LY 294,002), we found that SiRNA have similar effect with AKT inhibitors. Taking the results together, the current study shows that NECTIN4 has important biological implications in the tumorigenesis and metastasis of PTC and may be a potential therapeutic target for the disease.Keywords: NECTIN4, PTC, AKT |
| first_indexed | 2024-04-14T01:21:57Z |
| format | Article |
| id | doaj.art-cf2d6a9a8e654d7e87a2c5d6fb49285c |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-04-14T01:21:57Z |
| publishDate | 2019-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-cf2d6a9a8e654d7e87a2c5d6fb49285c2022-12-22T02:20:36ZengDove Medical PressCancer Management and Research1179-13222019-04-01Volume 112565257844880NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKTHao RTZheng CWu CYXia EJZhou XFQuan RDZhang XHRu-Tian Hao, Chen Zheng, Chen-Yong Wu, Er-Jie Xia, Xiao-Fen Zhou, Rui-Da Quan, Xiao-Hua ZhangDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou, Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaAbstract: Papillary thyroid cancer (PTC) is the most frequent type of malignant thyroid cancer, but its molecular mechanisms remain unknown. To better understand the tumorigenesis and progression of PTC, we conducted a comprehensive analysis of the whole-transcriptome resequencing of paired PTC and normal thyroid tissues. Nectin cell adhesion molecule 4 (NECTIN4) was significantly overexpressed in thyroid carcinoma compared with that in matched normal tissue. We also assessed the relation between the expression level of NECTIN4 and the clinicopathological features of PTC in The Cancer Genome Atlas database, and results showed that upregulated NECTIN4 is associated with lymph node metastasis (P<0.001) and tumor size (P=0.017). The biological function of NECTIN4 was also investigated by using the PTC cell lines TPC-1 and KTC-1. In vitro experiments demonstrated that NECTIN4 downregulation significantly inhibits the colony formation, proliferation, migration, and invasion of PTC cell lines. NECTIN4 could modulate the expression of epithelial–mesenchymal transition-related proteins via the PI3K/AKT pathway, and SC79, an AKT phosphorylation activator, could reverse the si-RNA knockdown effect. In addition, after the use of AKT inhibitors (LY 294,002), we found that SiRNA have similar effect with AKT inhibitors. Taking the results together, the current study shows that NECTIN4 has important biological implications in the tumorigenesis and metastasis of PTC and may be a potential therapeutic target for the disease.Keywords: NECTIN4, PTC, AKThttps://www.dovepress.com/nectin4-promotes-papillary-thyroid-cancer-cell-proliferation-migration-peer-reviewed-article-CMARNECTIN4 PTC AKT |
| spellingShingle | Hao RT Zheng C Wu CY Xia EJ Zhou XF Quan RD Zhang XH NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT Cancer Management and Research NECTIN4 PTC AKT |
| title | NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT |
| title_full | NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT |
| title_fullStr | NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT |
| title_full_unstemmed | NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT |
| title_short | NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT |
| title_sort | nectin4 promotes papillary thyroid cancer cell proliferation migration and invasion and triggers emt by activating akt |
| topic | NECTIN4 PTC AKT |
| url | https://www.dovepress.com/nectin4-promotes-papillary-thyroid-cancer-cell-proliferation-migration-peer-reviewed-article-CMAR |
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