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Updated: May 22, 2026
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Major Functional Transcriptome of an Inferred Center Regulator of an ER(-) Breast Cancer Model System
Li-Yu Daisy Liu1, Li-Yun Chang, Wen-Hung Kuo
1Department of Agronomy, Biometry Division, National Taiwan University, Taipei, Taiwan.
Abstract:
We aimed to find clinically relevant gene activities ruled by the signal transducer and activator of transcription 3 (STAT3) proteins in an ER(-) breast cancer population via network approach. STAT3 is negatively associated with both lymph nodal category and stage. MYC is a component of STAT3 network. MYC and STAT3 may co-regulate gene expressions for Warburg effect, stem cell like phenotype, cell proliferation and angiogenesis. We identified a STAT3 network in silico showing its ability in predicting its target gene expressions primarily for specific tumor subtype, tumor progression, treatment options and prognostic features. The aberrant expressions of MYC and STAT3 are enriched in triple negatives (TN). They promote histological grade, vascularity, metastasis and tumor anti-apoptotic activities. VEGFA, STAT3, FOXM1 and METAP2 are druggable targets. High levels of METAP2, MMP7, IGF2 and IGF2R are unfavorable prognostic factors. STAT3 is an inferred center regulator at early cancer development predominantly in TN.
Insights
Signal transducer and activator of transcription 3 (STAT3) protein networks regulate gene activity in ER(-) breast cancer. Aberrant STAT3 and MYC expression in triple-negative breast cancer drives tumor progression and suggests druggable targets.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Signal transducer and activator of transcription 3 (STAT3) proteins play a critical role in cellular processes.
- Understanding STAT3-regulated gene networks is crucial for advancing ER(-) breast cancer research.
- Aberrant STAT3 activity is implicated in various cancers, including triple-negative breast cancer (TNBC).
Purpose of the Study:
- To identify clinically relevant gene activities regulated by STAT3 in ER(-) breast cancer using a network approach.
- To investigate the co-regulatory roles of STAT3 and MYC in cancer hallmarks.
- To identify potential therapeutic targets within the STAT3 network.
Main Methods:
- In silico network analysis to identify STAT3-regulated genes.
- Correlation analysis between STAT3 network components and clinical parameters (lymph node status, tumor stage).
- Enrichment analysis of MYC and STAT3 in triple-negative breast cancer subtypes.
Main Results:
- STAT3 negatively correlates with lymph node category and tumor stage.
- MYC and STAT3 co-regulate genes involved in Warburg effect, stemness, proliferation, and angiogenesis.
- Aberrant MYC and STAT3 expression is enriched in TNBC, promoting histological grade, vascularity, metastasis, and anti-apoptotic activity.
- VEGFA, STAT3, FOXM1, and METAP2 identified as druggable targets.
- High METAP2, MMP7, IGF2, and IGF2R levels are unfavorable prognostic factors.
- STAT3 is an inferred central regulator in early TNBC development.
Conclusions:
- The STAT3 network effectively predicts gene expression related to tumor subtype, progression, treatment, and prognosis in ER(-) breast cancer.
- STAT3 and MYC are key regulators in TNBC, driving aggressive phenotypes and representing potential therapeutic targets.
- Specific genes within the network (METAP2, MMP7, IGF2, IGF2R) serve as prognostic biomarkers.
