# Characterize the role of EBF1 in breast cancer progression

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $349,988

## Abstract

Basal-like breast cancer (BLBC) is a devastating form with limited therapeutic options. During
tumor progression and metastasis, tumor cells rewire their metabolism, which results in an
enhanced nutrient uptake to supply the energetic and biosynthetic pathway under the hypoxic
condition. It is important for tumor cells to activate mitochondrial selective autophagy (mitophagy)
to avoid metabolic crisis and maintain the mitochondrial homeostasis. The means by which BLBC
cells fine-tune mitochondrial biogenesis and mitophagy to maintain metabolic and mitochondrial
homeostasis in order to adapt the hypoxic microenvironment, remain elusive. We found that EBF1
is highly expressed in BLBC. Knockdown of EBF1 induced extensive mitophagy, and eventual
cell death. Interestingly, silencing HIF1α blocked the EBF1 deficiency-induced mitophagy and cell
death in BLBC. In addition, we found that HIF1α induced EBF1 expression and that EBF1
interacted with HIF1α and inhibited HIF1α activity. Based on these preliminary data, we speculate
that EBF1 functions as a safeguard to ensure metabolic homeostasis through a regulation of
HIF1α activity, which, when compromised, can contribute to imbalanced mitochondria and
massive mitophagy in BLBC. Our strategy will be to first delineate the role of EBF1 in BLBC (Aim
1); then determine the molecular interplay between EBF1 and HIF1α (Aim 2); and to characterize
the role of EBF1 in vivo in human samples as well as in several mouse models (Aim 3). The
knowledge gained from these studies will increase our fundamental understanding about biologic
relationship between metabolic reprogramming and mitochondrial homeostasis, particular during
hypoxia. Our work also reveals a pivotal function for the EBF1 in BLBC and suggests that targeting
this pathway may offer alternative treatment strategies for this aggressive subtype of breast
cancer.

## Key facts

- **NIH application ID:** 10001467
- **Project number:** 5R01CA230758-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** YADI WU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $349,988
- **Award type:** 5
- **Project period:** 2018-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001467

## Citation

> US National Institutes of Health, RePORTER application 10001467, Characterize the role of EBF1 in breast cancer progression (5R01CA230758-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001467. Licensed CC0.

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