RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer.

NATALIA FERNÁNDEZ; SOFIA MARIA SOSA; JUSTIN T ROBERTS; MARIA SOL RECOUVREUX; LUCIANA ROCHA VIEGAS; JESSICA L CHRISTENSON; NICOLE S SPOELSTRA; FACUNDO LUIS COUTO; ANA RAIMONDI; JENNIFER K RICHER; NATALIA RUBINSTEIN.

BioRxiv

BioRxiv

Año: 2022

2692-8205

Background: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype for which no effective targeted therapies are available. Growing evidence suggests that chemotherapy-resistant cancer cells with stem-like properties (CSC) may repopulate the tumor. Androgen receptor (AR) is expressed in up to 50% of TNBC, and AR inhibition decreases CSC and tumor initiation. Runt-related transcription factor 1 (RUNX1) correlates with poor prognosis in TNBC and is regulated by AR in prostate cancer. Our group has shown that RUNX1 promotes TNBC cell migration and regulates tumor gene expression. We hypothesized that RUNX1 is regulated by AR and that both may work together in TNBC CSC to promote disease recurrence following chemotherapy. Results and methods: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) experiments in MDA-MB-453 revealed AR binding to RUNX1 regulatory regions. RUNX1 expression is upregulated by dihydrotestosterone (DHT) in MDA-MB-453 and in HCI-009 patient-derived xenograft (PDX) tumors (p