Abstract 2612: Roles of USF1 in breast tumorigenesis and disease progression

Abstract

Abstract Breast cancer accounts for nearly one-quarter of all cancer diagnoses and is the principal cause of cancer-related mortality in women worldwide. Triple negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer commonly resistant to therapeutics that have been successful in increasing survival in patients with ER+, PR+ and HER2+ breast cancer subtypes. As such, identifying factors that contribute to poor patient outcomes and mediate the growth and survival of TNBC cells remain important areas of investigation. USF1 (upstream stimulatory factor 1), a gene linked to drive lipogenesis and cellular proliferation, is overexpressed in human malignancies, yet its contribution to cancer remains unclear. In analyzing large number of genomic datasets including The Cancer Genome Atlas (TCGA), we found that USF1 expression is significantly higher in TNBC patient samples. Also, USF1 gene expression positively correlates with key lipogenic enzymes. Significantly, we found that high expression of USF1 in breast cancer correlates with decreased patient survival. We therefore hypothesize that USF1 promotes breast tumorigenesis and progression by activating lipogenic gene expression. We conducted pilot in vitro studies to determine the influence of USF1 expression and cell proliferation. It was demonstrated that knockdown of USF1 decreased cellular proliferation in 2D cell culture of the TNBC cell line MDA-MB-231. We also assessed the effects on USF1 expression levels on in vivo tumor growth. We found that USF1 overexpression and knockdown enhanced and reduced tumor growth in vivo, respectively. Further studies are underway to determine the mechanisms by which USF1 promotes TNBC tumorigenesis and metastatic progression. Our studies will shed lights on roles of USF1 in breast cancer tumor biology. (Supported by McKnight Foundation, Bankhead-Coley Cancer Research Program and James and Esther King Biomedical Research Program, Florida Department of Health.) Citation Format: Jessica Lewis, Iqbal Mahmud, Guimei Tian, Daiqing Liao. Roles of USF1 in breast tumorigenesis and disease progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2612.