# A novel strategy to debilitate breast cancer metastasis

> **NIH NIH R03** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $74,250

## Abstract

Abstract
Hypoxia is one of the key microenvironmental factors that impinges upon tumor progression and metastasis of
solid tumors such as breast cancer. While evaluating the impact of hypoxia, our group made an unanticipated
but striking observation that in chronic hypoxia, mammary tumors display a remarkable increase in the number
of nucleoli per cell. We found that this increase is concomitant with upregulated activity of the nucleolus. In the
nucleolus, RNA Pol I transcribes rDNA (contains the sequences of 18S, 5.8S and 28S rRNAs) to drive ribosome
biogenesis. We contend that this increased ribosome biogenesis is essential for hypoxic cell survival and
subsequent disease progression. In response to hypoxia, nucleolar ERK signaling activity is increased.
Increased ERK directly impinges upon the activity of UBF, a nucleolus-specific transcription activator, which
activates RNA Pol I. We contend that this increased nucleolar activity is a vulnerability of hypoxic tumor cells.
Our objective is to test an approach to exploit the dependence of hypoxic breast cancer cells on ERK activation.
We contend that debilitating the rRNA biogenesis following nucleolar ERK activation following hypoxic stress will
remarkably restrict the tumor growth and metastatic spread of breast cancer cells. To test this, we will adopt
carefully designed cellular and animal experimental approaches to test the effect of antagonizing ERK and RNA
Pol I activity on metastatic progression. Additionally, we will identify mechanistic details of nucleolar ERK
functions. Overall, our work will reveal novel aspects of nucleolar ERK response of tumor cells that support their
survival and metastatic ability under hypoxia.

## Key facts

- **NIH application ID:** 10672970
- **Project number:** 5R03CA267216-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Rajeev S Samant
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,250
- **Award type:** 5
- **Project period:** 2022-08-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10672970

## Citation

> US National Institutes of Health, RePORTER application 10672970, A novel strategy to debilitate breast cancer metastasis (5R03CA267216-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10672970. Licensed CC0.

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