# TAZ-driven Regulation of Tumor Microenvironment in Triple-Negative Breast Cancer

> **NIH NIH R03** · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · 2024 · $49,202

## Abstract

ABSTRACT
Breast cancer (BC) is a complex and heterogeneous neoplastic disease with a high incidence and mortality. BC
can be divided into clinical, histopathologic, and molecular subtypes. Triple-negative breast cancer (TNBC)
accounts for approximately 15% of all breast cancer cases and is characterized by tumors that do not express
the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).
TNBC is thought to be the most aggressive subtype and is associated with a poor prognosis, as well as a high
risk of distant recurrence and death within the first 3–5 years of follow-up. The absence of these receptors
renders TNBC resistant to treatments targeting those pathways. Thus, TNBC still remains a neoplastic disease
with unmet clinical challenges. Our laboratory has previously demonstrated an integral tumor-intrinsic role of
TAZ (transcriptional co-activator with PDZ-binding motif; also known as WWTR1), which is a key component of
the Hippo signaling pathway found in TNBC progression/metastasis. New preliminary data in our laboratory
indicate that tumor TAZ expression inhibits tumor progression in mouse models of TNBC cells in immune system
intact mice, thus indicating that TAZ expression also plays an underappreciated extrinsic role in TNBC biology.
We further revealed that TAZ regulates the recruitment and/or function of immune suppressive cells, such as
myeloid-derived suppressor cells (MDSCs), macrophages and regulatory T cells (Tregs). The overall objective
of this proposal is to understand the underlying molecular mechanisms by which TAZ expression in tumor cells
regulates immune suppressive cells in TNBC. Our central hypothesis is that tumor TAZ expression regulates the
TME landscape via cross-talk between cancer cells with non-cancer immune suppressive cells. Our long-term
goal is to decipher TAZ regulated crosstalk between breast tumor cells and the immune components within the
tumor microenvironment (TME) to uncover new prognostic or therapeutic targets for TNBC. To achieve these
goals, we propose the following two aims: 1) To determine the impact of tumor-intrinsic TAZ expression on the
immune-TME; and 2) To understand the molecular mechanisms of TAZ expression driven immune suppressive
cells recruitment in TME. A major impact of this study is to identify previously undescribed TAZ-mediated
mechanisms that will unveil new biomarkers or inform novel therapeutic interventions for advanced TNBC.

## Key facts

- **NIH application ID:** 11142069
- **Project number:** 7R03CA286634-02
- **Recipient organization:** UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
- **Principal Investigator:** Jianmin Zhang
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $49,202
- **Award type:** 7
- **Project period:** 2024-09-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11142069

## Citation

> US National Institutes of Health, RePORTER application 11142069, TAZ-driven Regulation of Tumor Microenvironment in Triple-Negative Breast Cancer (7R03CA286634-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11142069. Licensed CC0.

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