Related Experiment Video
Updated: Apr 21, 2026
Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies
Published on: July 3, 2025
Molecular profiling and computational network analysis of TAZ-mediated mammary tumorigenesis identifies actionable
Costa Frangou1, Ying-Wei Li1, He Shen1
1Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA.
Abstract:
Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancer (BC) cases and contributes disproportionately to BC mortality. TAZ, a key transducer of the Hippo pathway, has recently been demonstrated to confer breast cancer stem cell (CSC) traits. However, TAZ target genes and the underlying transcriptional regulatory pathways responsible for the CSC phenomenon remain unknown. Here, we demonstrate that the oncogenic activity of TAZ is essential for propagation of the malignant phenotype. We further show that constitutively active TAZ tumor-derived cells exhibit unique tumor-initiating properties, including increased self-renewal and metastatic seeding potential, acquired chemotherapy resistance and the ability to efficiently regenerate tumor formation in vivo. Combined digital RNA expression analysis and computational network approaches identify several signaling pathways that distinguish breast cancer tumor-initiating cells (T-ICs) from bulk tumor cells. We demonstrate the utility of this approach by repositioning the small molecule tyrosine kinase inhibitor, Dasatinib, which selectively targets T-ICs and inhibits TNBC growth in vivo.
Insights
This study reveals TAZ
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with high mortality.
- TAZ, a Hippo pathway transducer, promotes breast cancer stem cell (CSC) traits.
- TAZ's role in TNBC malignancy and its target genes remain unclear.
Purpose of the Study:
- To elucidate the oncogenic role of TAZ in TNBC.
- To identify TAZ target genes and regulatory pathways driving CSCs.
- To discover therapeutic strategies targeting TAZ-driven TNBC.
Main Methods:
- Analysis of constitutively active TAZ tumor-derived cells.
- Digital RNA expression analysis.
- Computational network approaches.
- Drug repositioning using small molecule inhibitors.
Main Results:
- Constitutively active TAZ enhances tumor initiation, self-renewal, metastasis, and chemoresistance.
- Identification of signaling pathways distinguishing TNBC tumor-initiating cells (T-ICs) from bulk tumor cells.
- Dasatinib selectively targets T-ICs and inhibits TNBC growth in vivo.
Conclusions:
- TAZ oncogenic activity is critical for TNBC malignant propagation.
- Targeting TAZ-driven pathways offers a novel therapeutic strategy for TNBC.
- Dasatinib shows promise in selectively inhibiting TNBC T-ICs.
