# The Role of FoxQ1 in Breast Cancer Chemoprevention by Allium Constituents - R01CA219180

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $357,994

## Abstract

ABSTRACT
Background: Breast cancer remains a leading cause of cancer-related deaths among women worldwide
despite our increasingly broader understanding of the biology, risk factors, and genomic landscape of the
disease. Chemoprevention signifies a meaningful strategy for reducing the morbidity and mortality from breast
cancer. Feasibility and promise of this approach is illustrated by continued clinical interest in selective estrogen
receptor (ER) modulators (e.g., tamoxifen), and more recently, aromatase inhibitors (e.g., exemestane) for
chemoprevention of luminal-type breast cancers. Unfortunately, these interventions have side effects and lack
activity against ER-negative subtypes of breast cancer (e.g., basal-like breast cancer). Therefore, a safe and
inexpensive chemopreventive intervention efficacious against different subtypes of breast cancer is still
desirable. The overarching goal of this preclinical research project is to acquire in vivo evidence for
chemopreventive efficacy of a highly promising dietary phytochemical (diallyl trisulfide; DATS) from Allium
vegetables (e.g., garlic) using rodent models exhibiting significant molecular overlap with basal-like and
luminal-type human breast cancers. In vivo evidence of chemopreventive efficacy in human-relevant animal
models is a prerequisite for initiation of clinical trials of DATS, which was well-tolerated in a prior first-in-human
interventional study with intermittent dosing schedule. Published work, including that from our laboratory,
already demonstrates activity of DATS against basal-like and luminal-type human breast cancer cell lines in
vitro, and their xenografts and cancer stem cell (bCSC) populations in vivo. Epidemiological studies have also
suggested an inverse association between dietary intake of garlic and onions and the risk of breast cancer.
The mechanistic aspects of this proposal are exceedingly novel and revolve around a still poorly understood
transcription factor, Forkhead box Q1 (FoxQ1). Benefitted by access to the RNA-Seq data from TCGA
database and through targeted gene expression profiling, we have identified novel targets of FoxQ1, including
Dachshund homolog 1 (DACH1) and monocarboxylate transporter 1 (MCT1). DACH1 is a cell fate
determination factor and tumor suppressor, whereas MCT1 has an oncogenic role in regulation of metabolic
reprogramming in cancer cells. Our recently published work indicates that FoxQ1 is a direct transcriptional
repressor of DACH1, and consequently FoxQ1 expression is inversely associated with that of DACH1 in
human breast cancers (TCGA). On the other hand, FoxQ1 expression is positively associated with that of
MCT1. We also found that DATS treatment suppresses FoxQ1 and MCT1 expression but induces DACH1
protein in breast cancer cells in vitro. However, the in vivo relevance of these cellular findings is still unclear.
Likewise, the contribution of FoxQ1/MCT1 axis to breast cancer progression and its potential role in cancer
chemop...

## Key facts

- **NIH application ID:** 9878797
- **Project number:** 5R01CA219180-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Shivendra Singh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,994
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878797

## Citation

> US National Institutes of Health, RePORTER application 9878797, The Role of FoxQ1 in Breast Cancer Chemoprevention by Allium Constituents - R01CA219180 (5R01CA219180-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9878797. Licensed CC0.

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