# Full Project 1: LSR Alters Metabolic Signaling to Drive Aggressive Breast Cancer Behaviors

> **NIH NIH U54** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $31,100

## Abstract

Project Summary/Abstract 
African American (AA) women have higher breast cancer mortality rates compared to other races. A greater 
prevalence of basal-like breast cancers in AA women explain some disparities, as these tumors are 
clinically the most aggressive, characterized by cancer stem No effective therapies exist and 
cell features. 
survival is poor. Escalating this disparity is the disease promoting effects of obesity, which is significantly 
higher in AA. The majority of studies on breast cancer disparities examine tumor characteristics, but the 
etiologic factors that lead to this disparity remain undefined. Our primary objective is to identify the 
mechanisms involved in promoting aggressive breast cancer in AAs, as a consequence of stromal effects at 
the site of the cancerous lesion. A key molecular pathway has been identified which integrates these 
clinical, microenvironmental and biological factors to affect tumor behavior. Aim 1 takes a novel approach, 
combining our published proteomic and gene expression datasets detailing race and tumor-subtype specific 
stromal interactions with our recently published data on the identified pathway promoting cancer stem cell- 
like, aggressive behaviors. Aims 2 and 3 extend these data to experimental studies to elucidate mechanistic 
details. To accomplish these tasks, our team established research partnerships that provides access to 
resources including the Normal Breast Study: a unique epidemiologic study from ethnically diverse patients 
at UNC Hospitals. There are several important biological implications of this work. The observation that AA 
breast tissue is enriched with distinct proteins, the prevalence of obesity in AA, and the predisposition to 
develop basal-like tumors strongly suggests a biological link between race, metabolism and cancer subtype. 
The role of differentially regulated metabolic-sensitive proteins in the tumor microenvironment will provide 
novel insights into the biological basis of racial disparities. The long-term goal of our collaboration is to 
understand tumor-microenvironment interactions and their influence on breast cancer disparities. Our 
distinctive approach will expose unique characteristics of the breast tissue microenvironment and will 
integrate advances in the field of tumor microenvironment with health disparities research. 
Relevance 
This proposal addresses breast cancer disparities by studying a key pathway that drive the aggressiveness 
of breast cancers. By combining observational studies on differences in this pathway by race, BMI, and 
breast cancer subtype with experimental studies to understand the role of this pathway in cellular 
phenotypes, this project will provide important and novel insight into the biological basis of racial disparities.

## Key facts

- **NIH application ID:** 10247134
- **Project number:** 3U54CA156733-10S1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Keith Burridge
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,100
- **Award type:** 3
- **Project period:** 2010-09-28 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247134

## Citation

> US National Institutes of Health, RePORTER application 10247134, Full Project 1: LSR Alters Metabolic Signaling to Drive Aggressive Breast Cancer Behaviors (3U54CA156733-10S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10247134. Licensed CC0.

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