# Cancer cell fusion; A mechanism driving breast tumor heterogeneity and metastasis

> **NIH NIH U54** · JACKSON STATE UNIVERSITY · 2024 · $193,281

## Abstract

Project Summary/Abstract 
 Approximately 90% of breast cancer-related deaths are caused by local invasion and distant metastasis of 
tumor cells. While invasive breast cancer incidence rates have been stabilized in white women in the recent 
decade, a steady increase in the incidence rates by 0.3% per year has been observed in black women. 
Meanwhile, the survival rates for invasive breast cancer have increased for both populations over time. 
However, they remain 10% lower for black women. Although the reasons for these disparities are multifactorial, 
differences in molecular mechanisms and signaling pathways driving the progression of the disease might 
account at least in part for the survival disparity. Triple negative breast cancer is more common in black 
women and was shown to exhibit extensive genomic heterogeneity and resistance to drug. In this study, we 
assess cancer cell fusion as a mechanism driving tumor heterogeneity and metastasis and a potential basis for 
the disproportion in breast cancer heterogeneity between white and black women. Different hypotheses have 
been put forward as to how metastasis develops. However, exactly how each of the mechanisms proposed so 
far is accomplished is yet to be established. Studies have suggested that metastatic cells result from the fusion 
of primary tumor cells and cells of hematopoietic lineage. Some reports including ours showed that fusion 
enables rapid diversification and subsequent intra-tumor heterogeneity supportive of metastasis. We observed 
that breast cancer cell fusion happens in vivo and contributes to metastasis. We also showed that fusion 
between non metastatic breast cancer cells and mesenchymal/multipotent stem/stromal cells (MSCs) was 
enhanced with hypoxia by a mechanism involving apoptosis and dependent of the phosphatidyl-serine 
(PtdSer) receptor BAI1. BAI1 and apoptotic cells were recently identified as new promoters of myoblast fusion 
by means of signaling through ELMO/Dock180/Rac1 pathway. The ELMO/Dock180/Rac1 pathway is activated 
in breast cancer. We therefore hypothesize that hypoxia stress-induced apoptosis in primary tumors 
stimulates fusion between tumor cells and cells of the tumor microenvironment by a mechanism involving BAI1 
activation and signals through ELMO/Dock180/Rac1 pathway. Our objective is to investigate the role of 
BAI1/ELMO/Dock180/Rac1 pathway in the mechanism of fusion of breast tumor cells isolated from both white 
and black women with MSCs in vitro. We will also determine the function of BAI1 in breast cancer metastasis 
in vivo by analyzing the ability of breast specific Bai1 knockout mice in the FVB/N-Tg(MMTVPyVT)634Mul/J 
background to develop breast cancer metastasis. The completion of this study would contribute to delineating 
the mechanisms of cancer cell fusion, the role of cancer cell fusion in the development of molecular diversity in 
breast tumors, and potentially the mechanisms of metastases. This study might provide new...

## Key facts

- **NIH application ID:** 10857030
- **Project number:** 5U54MD015929-05
- **Recipient organization:** JACKSON STATE UNIVERSITY
- **Principal Investigator:** Felicite K Noubissi
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $193,281
- **Award type:** 5
- **Project period:** 2020-09-08 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10857030

## Citation

> US National Institutes of Health, RePORTER application 10857030, Cancer cell fusion; A mechanism driving breast tumor heterogeneity and metastasis (5U54MD015929-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10857030. Licensed CC0.

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