Format

Send to

Choose Destination
Oncogene. 2018 Apr;37(15):2008-2021. doi: 10.1038/s41388-017-0042-x. Epub 2018 Jan 25.

Network analysis of SRC-1 reveals a novel transcription factor hub which regulates endocrine resistant breast cancer.

Author information

1
Endocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons, Dublin, Ireland.
2
Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK.
3
Endocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons, Dublin, Ireland. lyoung@rcsi.ie.

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.

PMID:
29367763
PMCID:
PMC5895607
DOI:
10.1038/s41388-017-0042-x
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center