Novel mechanistic targets of forkhead box Q1 transcription factor in human breast cancer cells.

Abstract

The transcription factor forkhead box Q1 (FoxQ1) is overexpressed in different solid tumors including breast cancer, but the mechanism underlying its oncogenic function is still not fully understood. In this study, we compared RNA-seq data from FoxQ1 overexpressing SUM159 cells with that of empty vector-transfected control cells to identify novel mechanistic targets of this transcription factor. Analysis of The Cancer Genome Atlas (TCGA) data set revealed significantly higher expression of FoxQ1 in black breast cancer patients compared with white women with this disease. In contrast, expression of FoxQ1 was comparable in ductal and lobular carcinomas in the breast cancer TCGA data set. Complementing our published findings in basal-like subtype, immunohistochemistry revealed upregulation of FoxQ1 protein in luminal-type human breast cancer tissue microarrays when compared with normal mammary tissues. Many previously reported transcriptional targets of FoxQ1 (eg, E-cadherin, N-cadherin, fibronectin 1, etc) were verified from the RNA-seq analysis. FoxQ1 overexpression resulted in the downregulation of genes associated with cell cycle checkpoints, M phase, and cellular response to stress/external stimuli as evidenced from the Reactome pathway analysis. Consequently, FoxQ1 overexpression resulted in mitotic arrest in basal-like SUM159 and human mammary epithelial cell line, but not in luminal-type MCF-7 cells. Finally, we show for the first time that FoxQ1 is a direct transcriptional regulator of interleukin (IL)-1α, IL-8, and vascular endothelial growth factor in breast cancer cells as evidenced by chromatin immunoprecipitation assay. In conclusion, the present study reports novel mechanistic targets of FoxQ1 in human breast cancer cells.

• Authors: Su-Hyeong Kim, Eun-Ryeong Hahm, Krishna B Singh, Shivendra V Singh
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 59 Issue 10 Pg. 1116-1128 (10 2020) ISSN: 1098-2744 [Electronic] United States
• PMID: 32754922 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2020 Wiley Periodicals LLC.

Chemical References

• Biomarkers, Tumor
• CXCL8 protein, human
• FOXQ1 protein, human
• Forkhead Transcription Factors
• IL1A protein, human
• Interleukin-1alpha
• Interleukin-8
• VEGFA protein, human
• Vascular Endothelial Growth Factor A

Topics

• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Cycle
• Cell Movement
• Cell Proliferation
• Female
• Forkhead Transcription Factors (genetics, metabolism)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Interleukin-1alpha (genetics, metabolism)
• Interleukin-8 (genetics, metabolism)
• Prognosis
• Tumor Cells, Cultured
• Vascular Endothelial Growth Factor A (genetics, metabolism)