TOP2A Promotes Cell Migration, Invasion and Epithelial-Mesenchymal Transition in Cervical Cancer via Activating the PI3K/AKT Signaling

• Published in: Cancer management and research 2020-01, Vol.12, p.3807-3814
• Main Authors: Wang, Bi, Shen, Yaping, Zou, Yin, Qi, Zhengjun, Huang, Guijia, Xia, Shan, Gao, Rui, Li, Fenghu, Huang, Zhi
• Format: Article
• Language: English
• Subjects: cell morphology; Cervical cancer; Development and progression; epithelial‑mesenchymal transition; migration; Original Research; pi3k/akt signaling; Stem cells; topoisomerases type iia
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S240577

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. 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. 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. 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.