FOXP3 Inhibits the Metastasis of Breast Cancer by Downregulating the Expression of MTA1

• Published in: Frontiers in oncology Vol. 11; p. 656190
• Main Authors: Liu, Chenlin, Han, Jun, Li, Xiaoju, Huang, Tonglie, Gao, Yuan, Wang, Baolong, Zhang, Kuo, Wang, Shuning, Zhang, Wangqian, Li, Weina, Hao, Qiang, Li, Meng, Zhang, Yingqi, Zhang, Cun
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 07.07.2021
• Subjects: breast cancer; FOXP3; metastasis; MTA1; Oncology; transcription factor
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2021.656190

Background FOXP3, as a tumour suppressor gene, has a vital function in inhibiting the metastasis of breast cancer cells, but the mechanisms by which it inhibits metastasis have not been fully elucidated. This study intended to explore a new mechanism by which FOXP3 inhibits breast cancer metastasis. Methods Bioinformatic analysis was performed to identify potential downstream molecules of FOXP3. The function of FOXP3 in inhibiting MTA1 expression at the mRNA and protein levels was verified by real-time PCR and Western blot analysis. The interaction between FOXP3 and the MTA1 promoter was verified by transcriptomic experiments. In vitro and in vivo experiments were used to determine whether the regulation of MTA1 by FOXP3 affected the invasion and migration of breast cancer cells. Immunohistochemistry was adopted to explore the correlation between the expression levels of FOXP3 and MTA1 in breast cancer samples. Results Bioinformatics-based sequencing suggested that MTA1 is a potential downstream molecule of FOXP3. FOXP3 downregulated the expression of MTA1 in breast cancer cells by directly inhibiting MTA1 promoter activity. Importantly, FOXP3’s regulation of MTA1 affected the ability of breast cancer cells to invade and metastasize in vitro and in vivo . Moreover, analysis of clinical specimens showed a significant negative correlation between the expression levels of FOXP3 and MTA1 in breast cancer. Conclusion We systematically explored a new mechanism by which FOXP3 inhibits breast cancer metastasis via the FOXP3-MTA1 pathway.