FLOT2 Promotes the Proliferation and Epithelial-mesenchymal Transition of Cervical Cancer by Activating the MEK/ERK1/2 Pathway

Background: As prevalent cancer in women, approximately 569,847 cases of cervical cancer occur every year. Aims: This study aimed to explore the role of FLOT2 and its related mechanism in the development of cervical cancer. Study Design: Cell culture study and animal experimentation. Methods: Quantitative reverse-transcription polymerase chain reaction PCR and Western blot analysis were performed to evaluate the expression of FLOT2. Flow cytometry was applied for the evaluation of cell apoptosis. Cell Counting Kit-8 and colony formation were utilized for proliferation measurement. Cervical cancer mice model was employed to measure the role of FLOT2 in vivo. Results: FLOT2 mRNA and protein levels were dramatically elevated (P < 0.001) in cervical cancer cell line HcerEpic cells. The cell viability and proliferation of cervical cancer cells were enhanced (P < 0.01) by overexpression of FLOT2 and reduced (P < 0.01) by FLOT2 downregulation. In addition, FLOT2 overexpression elevated (P < 0.01) the cell migration abilities of cervical cancer cells, whereas its depletion inhibited (P < 0.01) the cell migration abilities. Moreover, the protein expression of epithelial-mesenchymal transition markers including Vimentin, N-cadherin, and E-cadherin were assessed, and the results showed enhanced Vimentin and N-cadherin levels (P < 0.05) by FLOT2 upregulation and declined (P < 0.01) by FLOT2 downregulation. FLOT2 upregulation reduced (P < 0.05) the level of E-cadherin protein, whereas FLOT2 suppression attenuated this effect (P < 0.05). Furthermore, FLOT2 increased (P < 0.05) p-MEK/MEK, p-ERK1/2/ERK1/2, and p-AKT/AKT levels to activate the MEK/ ERK1/2 and AKT pathways in cervical cancer. Finally, our results indicated that FLOT2 inhibited (P < 0.001) cervical cancer growth in vivo. Conclusion: FLOT2 aggravates the proliferation and epithelial mesenchymal transition of cervical cancer by activating the MEK/ ERK1/2 and AKT pathways.

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