# Exploration of the immunosuppressive function of RBMS3/PRRX1 axis in TNBC

> **NIH NIH R21** · WAYNE STATE UNIVERSITY · 2024 · $205,187

## Abstract

Abstract
The epithelial to mesenchymal transition (EMT), a developmental process related to tissue repair and
pathological processes, has been found to occur in the progression of carcinomas to invasive and
metastatic disease. Accumulated evidence suggests the EMT could contribute to the
immunosuppressive function of cancer cells. However, the underlying molecular mechanism linking
EMT and immunosuppressive function in cancer remain largely unknown.
To tackle this problem, our research group developed an integrative transcriptomic approach to
combine expression profiling of breast cancer cell lines and several mammary epithelial cell EMT
models. This screen identified RNA-binding motif single-stranded interacting protein 3 (RBMS3) as
being significantly and reproducibly associated with EMT. We further showed that RBMS3 stabilized
a group of EMT-related genes, including PRRX1. Functional analysis demonstrated the
RBMS3/PRRX1 axis is responsible for maintaining mesenchymal status and motility properties of
breast cancer cells, as well as controlling a group of pro- inflammatory cytokines. More importantly,
knockdown of RBMS3 in TNBC MDA-MB231 cells results in a significant delay of tumorigenesis in
vivo, which is not observed in vitro. These results indicate RBMS3 mediates breast cancer
progression, potentially by simultaneously increasing invasive potential and promoting an
immunosuppressed tumor microenvironment. In this study, we propose to investigate the effect of
RBMS3/PRRX1 axis on immunosuppression and breast cancer progression in immunocompetent
animal models and explore the potential impact of targeting RBMS3/PRRX1 axis in facilitating
immunotherapy in TNBC models.
We expect the proposed studies to be completed within two years, with two critical outcomes: 1)
revealing the role of RBMS3/PRRX1 axis in driving TNBC progression through detailed analysis of the
alterations of immune- microenvironment; 2) proof-of-concept evidence that targeting
RBMS3/PRRX1 axis will facilitate immunotherapy for TNBC treatment. These results will lay a solid
foundation for further development of specific targeting RBMS3/PRRX1axis for treatment of TNBC.
By achieving these goals, we will be able to address the following overarching challenges: 1) identify
why some breast cancers become life-threatening metastases; and 2) eliminate or reduce the
mortality associated with metastatic breast cancer.

## Key facts

- **NIH application ID:** 10828417
- **Project number:** 5R21CA273771-02
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Heather Marie Gibson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $205,187
- **Award type:** 5
- **Project period:** 2023-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828417

## Citation

> US National Institutes of Health, RePORTER application 10828417, Exploration of the immunosuppressive function of RBMS3/PRRX1 axis in TNBC (5R21CA273771-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10828417. Licensed CC0.

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