Back to Journals » Cancer Management and Research » Volume 10

Downregulation of FOXO6 in breast cancer promotes epithelial–mesenchymal transition and facilitates migration and proliferation of cancer cells

Authors Ye H, Duan M

Received 21 November 2017

Accepted for publication 3 March 2018

Published 30 October 2018 Volume 2018:10 Pages 5145—5156

DOI https://doi.org/10.2147/CMAR.S157661

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Leylah Drusbosky


Hui Ye,1 Meiling Duan2

1Department of Galactophore, Linyi Central Hospital of Shandong, Linyi, People’s Republic of China; 2Department of Respiratory One, Linyi Central Hospital of Shandong, Linyi, People’s Republic of China

Purpose: Increasing evidence indicates that members of forkhead transcription factor family (FOXO) play key roles in cell proliferation and apoptosis in multiple cancers, including prostate cancer. However, the underlying mechanism of FOXO6 was not yet known. The aim of our work is to investigate the function of FOXO6 in breast cancer.
Methods: In the present study, quantitative real-time polymerase chain reaction and Western blotting analyses were used to detect the expression of FOXO6 in breast cancer tissues and cell lines.
Results: The results revealed that FOXO6 was downregulated in breast cancer tissues and cell lines, compared with adjacent normal tissues and MCF-10A cells, respectively. Moreover, the expression of FOXO6 was associated with the expression of epithelial–mesenchymal transition (EMT) indicator proteins, such as E-cadherin and N-cadherin. Additionally, our findings suggested that FOXO6 expression was negatively associated with tumor size (p=0.002), pathological grade (p=0.018) and lymph node metastasis (p=0.003). Sirt6 has been found to promote cell proliferation and metastasis in several cancers, and quantitative chromatin immunoprecipitation and luciferase reporter assays indicated FOXO6 transcriptionally regulated Sirt6 expression. Furthermore, various functional experiments, including wound healing assay, transwell invasion assay, colony formation assay and Cell Counting Kit-8 assay, revealed that FOXO6 suppressed cell migration, invasion, and proliferation of breast cancer cells.
Conclusion: In conclusion, FOXO6 serves as a tumor suppressor in breast cancer, and suppresses EMT through regulation of Sirt6.

Keywords: FOXO6, EMT, Sirt6, migration, breast cancer

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]