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

Abstract

BackgroundFOXP3, 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.MethodsBioinformatic 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.ResultsBioinformatics-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.ConclusionWe systematically explored a new mechanism by which FOXP3 inhibits breast cancer metastasis via the FOXP3-MTA1 pathway.

The expression landscape of FOXP3 and its prognostic value in breast cancer

“…Nuclear FOXP3 expression was verified as an independent favorable factor for OS in BRCA, especially in TNBC. This finding is essentially consistent with recent studies (12,13).…”

“…This ability of transcriptional regulation may well be the potential superiority of FOXP3 in relative to prior biomarkers of BC. It has been reported that FOXP3 can inhibit the transcription of the proto-oncogene HER2 (10) and the expression of runt-related transcription factor 1 (RUNX1) (11), vascular endothelial growth factor (VEGF) (12), and metastasis-associated 1 (MTA1) (13) to perform its anticancer function in BC. However, the biological function and molecular mechanism of FOXP3 in BC have not been fully illustrated.…”

The Role of FOXP3 on Tumor Metastasis and Its Interaction with Traditional Chinese Medicine

“…Clinical specimen analyses also showed a negative relationship between VEGF and nuclear FOXP3 expression. A similar pathomechanism was found by Liu et al [ 31 ], they revealed that FOXP3 can bind to the MTA1 (metastasis-associated 1) promoter and downregulate the transcriptional activity of the MTA1 gene. MTA1 influences local invasion and lymph-node metastasis and regulates downstream gene transcription activity.…”

Human FOXP3 and tumour microenvironment

“…For example, FOXP3 can directly bind to the promoter of CD44 and inhibit its protein expression, thereby inhibiting the adhesion, invasion and metastasis of human breast cancer cells [49]. In addition, FOXP3 can downregulate the expression of Metastasis-associated 1 (MTA1) in breast cancer cells by directly inhibiting the activity of the MTA1 promoter, affecting the ability of breast cancer cells to invade and metastasize in vitro and in vivo [50].…”