TOP2A Promotes Cell Migration, Invasion and Epithelial–Mesenchymal Transition in Cervical Cancer via Activating the PI3K/AKT Signaling
Bi Wang,1,2,* Yaping Shen,3,* Yin Zou,4 Zhengjun Qi,4 Guijia Huang,4 Shan Xia,5 Rui Gao,6 Fenghu Li,5 Zhi Huang7 1Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Paediatrics, Mate...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2020-05-01
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| Series: | Cancer Management and Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/top2a-promotes-cell-migration-invasion-and-epithelialndashmesenchymal--peer-reviewed-article-CMAR |
| _version_ | 1819019877274353664 |
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| author | Wang B Shen Y Zou Y Qi Z Huang G Xia S Gao R Li F Huang Z |
| author_facet | Wang B Shen Y Zou Y Qi Z Huang G Xia S Gao R Li F Huang Z |
| author_sort | Wang B |
| collection | DOAJ |
| description | Bi Wang,1,2,* Yaping Shen,3,* Yin Zou,4 Zhengjun Qi,4 Guijia Huang,4 Shan Xia,5 Rui Gao,6 Fenghu Li,5 Zhi Huang7 1Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Paediatrics, Maternal and Child Health Hospital of Guiyang City, Guiyang, Guizhou, People’s Republic of China; 3Department of Interventional Radiology, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 4Department of Oncology, The Second Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 5Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 6Guiyang Customs Guizhou International Travel Healthcare Center, Guiyang, Guizhou, People’s Republic of China; 7Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fenghu LiDepartment of Gynecologic Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang City, Guizhou Province, People’s Republic of ChinaEmail fenghuli19@163.comZhi HuangDepartment of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang City, Guizhou Province, People’s Republic of ChinaEmail doctor@huangzhi.comBackground/Objective: Topoisomerases type IIA (TOP2A) was identified to present with a high-expression pattern in cervical cancer. However, TOP2A role in the progression of cervical cancer remains unknown. Here, we aimed to explore the effect and reveal the underlying mechanism of TOP2A in the migration, invasion and epithelial–mesenchymal transition (EMT) of cervical cancer.Materials and Methods: The expression profiles of TOP2A in 20 paired cervical cancer tissues and the paracancerous normal tissues were detected by using Western blotting assay. Transwell chambers were used to test cell migration and invasion abilities. Cell morphology and the expressions of E-cadherin and N-cadherin were detected to assess cell EMT. LY294002 was used to inhibit the activation of PI3K/AKT signaling.Results: Compared with the paracancerous normal tissues, TOP2A was overexpressed in 85% (17/20) cervical cancer tissues. Repression of TOP2A expression in SiHa cells significantly weakened cell migration and invasion abilities, reduced cell numbers in shuttle shape and increased E-cadherin expression while decreased E-cadherin expression. To the opposite, overexpression of TOP2A in Hela cells induced opposite results. In addition, the expression of p-AKT was increased when TOP2A was overexpressed in Hela cells, and p-AKT expression was decreased when TOP2A was silenced in SiHa cells. Moreover, suppression of the PI3K/AKT signaling with LY294002 treatment apparently rescued TOP2A-mediated promotions in cell migration, invasion and EMT in Hela cells.Conclusion: This study reveals that TOP2A is abnormally overexpressed in cervical cancer tissues, and TOP2A overexpression leads to cell migration, invasion and EMT via activating PI3K/AKT signaling.Keywords: topoisomerases type IIA, epithelial–mesenchymal transition, cell morphology, migration, PI3K/AKT signaling |
| first_indexed | 2024-12-21T03:42:17Z |
| format | Article |
| id | doaj.art-b4ee7802bf8d42c6a4f4007c7454e933 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-21T03:42:17Z |
| publishDate | 2020-05-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-b4ee7802bf8d42c6a4f4007c7454e9332022-12-21T19:17:11ZengDove Medical PressCancer Management and Research1179-13222020-05-01Volume 123807381453990TOP2A Promotes Cell Migration, Invasion and Epithelial–Mesenchymal Transition in Cervical Cancer via Activating the PI3K/AKT SignalingWang BShen YZou YQi ZHuang GXia SGao RLi FHuang ZBi Wang,1,2,* Yaping Shen,3,* Yin Zou,4 Zhengjun Qi,4 Guijia Huang,4 Shan Xia,5 Rui Gao,6 Fenghu Li,5 Zhi Huang7 1Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Paediatrics, Maternal and Child Health Hospital of Guiyang City, Guiyang, Guizhou, People’s Republic of China; 3Department of Interventional Radiology, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 4Department of Oncology, The Second Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 5Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 6Guiyang Customs Guizhou International Travel Healthcare Center, Guiyang, Guizhou, People’s Republic of China; 7Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fenghu LiDepartment of Gynecologic Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang City, Guizhou Province, People’s Republic of ChinaEmail fenghuli19@163.comZhi HuangDepartment of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang City, Guizhou Province, People’s Republic of ChinaEmail doctor@huangzhi.comBackground/Objective: Topoisomerases type IIA (TOP2A) was identified to present with a high-expression pattern in cervical cancer. However, TOP2A role in the progression of cervical cancer remains unknown. Here, we aimed to explore the effect and reveal the underlying mechanism of TOP2A in the migration, invasion and epithelial–mesenchymal transition (EMT) of cervical cancer.Materials and Methods: The expression profiles of TOP2A in 20 paired cervical cancer tissues and the paracancerous normal tissues were detected by using Western blotting assay. Transwell chambers were used to test cell migration and invasion abilities. Cell morphology and the expressions of E-cadherin and N-cadherin were detected to assess cell EMT. LY294002 was used to inhibit the activation of PI3K/AKT signaling.Results: Compared with the paracancerous normal tissues, TOP2A was overexpressed in 85% (17/20) cervical cancer tissues. Repression of TOP2A expression in SiHa cells significantly weakened cell migration and invasion abilities, reduced cell numbers in shuttle shape and increased E-cadherin expression while decreased E-cadherin expression. To the opposite, overexpression of TOP2A in Hela cells induced opposite results. In addition, the expression of p-AKT was increased when TOP2A was overexpressed in Hela cells, and p-AKT expression was decreased when TOP2A was silenced in SiHa cells. Moreover, suppression of the PI3K/AKT signaling with LY294002 treatment apparently rescued TOP2A-mediated promotions in cell migration, invasion and EMT in Hela cells.Conclusion: This study reveals that TOP2A is abnormally overexpressed in cervical cancer tissues, and TOP2A overexpression leads to cell migration, invasion and EMT via activating PI3K/AKT signaling.Keywords: topoisomerases type IIA, epithelial–mesenchymal transition, cell morphology, migration, PI3K/AKT signalinghttps://www.dovepress.com/top2a-promotes-cell-migration-invasion-and-epithelialndashmesenchymal--peer-reviewed-article-CMARtopoisomerases type iiaepithelial‑mesenchymal transitioncell morphologymigrationpi3k/akt signaling |
| spellingShingle | Wang B Shen Y Zou Y Qi Z Huang G Xia S Gao R Li F Huang Z TOP2A Promotes Cell Migration, Invasion and Epithelial–Mesenchymal Transition in Cervical Cancer via Activating the PI3K/AKT Signaling Cancer Management and Research topoisomerases type iia epithelial‑mesenchymal transition cell morphology migration pi3k/akt signaling |
| title | TOP2A Promotes Cell Migration, Invasion and Epithelial–Mesenchymal Transition in Cervical Cancer via Activating the PI3K/AKT Signaling |
| title_full | TOP2A Promotes Cell Migration, Invasion and Epithelial–Mesenchymal Transition in Cervical Cancer via Activating the PI3K/AKT Signaling |
| title_fullStr | TOP2A Promotes Cell Migration, Invasion and Epithelial–Mesenchymal Transition in Cervical Cancer via Activating the PI3K/AKT Signaling |
| title_full_unstemmed | TOP2A Promotes Cell Migration, Invasion and Epithelial–Mesenchymal Transition in Cervical Cancer via Activating the PI3K/AKT Signaling |
| title_short | TOP2A Promotes Cell Migration, Invasion and Epithelial–Mesenchymal Transition in Cervical Cancer via Activating the PI3K/AKT Signaling |
| title_sort | top2a promotes cell migration invasion and epithelial ndash mesenchymal transition in cervical cancer via activating the pi3k akt signaling |
| topic | topoisomerases type iia epithelial‑mesenchymal transition cell morphology migration pi3k/akt signaling |
| url | https://www.dovepress.com/top2a-promotes-cell-migration-invasion-and-epithelialndashmesenchymal--peer-reviewed-article-CMAR |
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