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Updated: Feb 15, 2026
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Network analysis of SRC-1 reveals a novel transcription factor hub which regulates endocrine resistant breast cancer
Alacoque L Browne1, Sara Charmsaz1, Damir Varešlija1
1Endocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons, Dublin, Ireland.
Abstract:
Steroid receptor coactivator 1 (SRC-1) interacts with nuclear receptors and other transcription factors (TFs) to initiate transcriptional networks and regulate downstream genes which enable the cancer cell to evade therapy and metastasise. Here we took a top-down discovery approach to map out the SRC-1 transcriptional network in endocrine resistant breast cancer. First, rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) was employed to uncover new SRC-1 TF partners. Next, RNA sequencing (RNAseq) was undertaken to investigate SRC-1 TF target genes. Molecular and patient-derived xenograft studies confirmed STAT1 as a new SRC-1 TF partner, important in the regulation of a cadre of four SRC-1 transcription targets, NFIA, SMAD2, E2F7 and ASCL1. Extended network analysis identified a downstream 79 gene network, the clinical relevance of which was investigated in RNAseq studies from matched primary and local-recurrence tumours from endocrine resistant patients. We propose that SRC-1 can partner with STAT1 independently of the estrogen receptor to initiate a transcriptional cascade and control regulation of key endocrine resistant genes.
Insights
Steroid receptor coactivator 1 (SRC-1) partners with STAT1 to regulate key genes in endocrine-resistant breast cancer, driving therapy evasion and metastasis. This SRC-1-STAT1 network is crucial for cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Steroid receptor coactivator 1 (SRC-1) is vital for transcriptional regulation.
- SRC-1's role in endocrine-resistant breast cancer and metastasis is not fully understood.
- Identifying SRC-1's transcriptional partners and targets is key to understanding cancer progression.
Purpose of the Study:
- To map the SRC-1 transcriptional network in endocrine-resistant breast cancer.
- To identify novel SRC-1 transcription factor (TF) partners and their target genes.
- To investigate the clinical relevance of the SRC-1 network in patient tumors.
Main Methods:
- Rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) to identify SRC-1 interacting proteins.
- RNA sequencing (RNAseq) to identify SRC-1 target genes.
- Molecular and patient-derived xenograft studies to validate findings.
- Network analysis and clinical data analysis from patient tumors.
Main Results:
- STAT1 was identified as a novel SRC-1 TF partner.
- SRC-1 and STAT1 regulate four key transcription targets: NFIA, SMAD2, E2F7, and ASCL1.
- A 79-gene downstream network regulated by SRC-1 was identified.
- The SRC-1 network's clinical relevance was confirmed in endocrine-resistant tumors.
Conclusions:
- SRC-1 can partner with STAT1 independently of estrogen receptor signaling.
- This SRC-1-STAT1 interaction initiates a transcriptional cascade.
- The identified network is critical for regulating key genes in endocrine-resistant breast cancer, promoting therapeutic evasion and metastasis.
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