GSE120685
The Role of the RNA-binding protein HuR in MPNST growth and metastasis [RNA-seq]
Oncogenic gene expression programs are essential for the development and maintenance of the cancer phenotype. An emerging view is that cancer cells can develop a strong addiction to discrete molecular regulators that control these aberrant transcription programs, making these attractive targets for effective and enduring therapies. Here, we identify the RNA-binding protein HuR as a central oncogenic driver for Malignant peripheral nerve sheath tumours (MPNSTs), which are highly aggressive sarcomas that originate from cells of the Schwann cell lineage. These neoplasms are strongly metastatic, resistant to radio-and chemotherapy and are typically fatal with no effective treatment. We find that HuR is highly elevated and binds to a multitude of cancer-associated transcripts in human MPNST samples. HuR inhibition has potent cytostatic and cytotoxic effects on tumour growth, and strongly supresses their metastatic capacity in vivo. Importantly, we find that the profound anti-tumorigenic effects of HuR stems from its unique ability to regulate multiple key oncogenic signals that ultimately converge on highly intricate transcription regulatory networks that coordinate the core biological capabilities of MPNST cells. The exceptional dependency on HuR thus confers a competitive advantage to MPNST cells for their survival, proliferation and dissemination, representing an ideal target that could be exploited for MPNST treatment. Overall design: Gene expression changes after HuR silencing in MPNST cell line ST88-14