Retinoic acid and TGF-β signalling cooperate to overcome MYCN-induced retinoid resistance.

ABSTRACT:

Background

Retinoid therapy is widely employed in clinical oncology to differentiate malignant cells into their more benign counterparts. However, certain high-risk cohorts, such as patients with MYCN-amplified neuroblastoma, are innately resistant to retinoid therapy. Therefore, we employed a precision medicine approach to globally profile the retinoid signalling response and to determine how an excess of cellular MYCN antagonises these signalling events to prevent differentiation and confer resistance.

Methods

We applied RNA sequencing (RNA-seq) and interaction proteomics coupled with network-based systems level analysis to identify targetable vulnerabilities of MYCN-mediated retinoid resistance. We altered MYCN expression levels in a MYCN-inducible neuroblastoma cell line

SUBMITTER: Duffy DJ 

PROVIDER: S-EPMC5303304 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature