Palomo-Irigoyen, M;
Pérez-Andrés, E;
Iruarrizaga-Lejarreta, M;
Barreira Manrique, A;
Tamayo-Caro, M;
Vila-Vecilla, L;
Moreno-Cugnon, L;
... Woodhoo, A; + view all
(2020)
HuR/ELAVL1 drives malignant peripheral nerve sheath tumour growth and metastasis.
Journal of Clinical Investigation
10.1172/JCI130379.
(In press).
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Abstract
Cancer cells can develop a strong addiction to discrete molecular regulators, which control the aberrant gene expression programs that drive and maintain the cancer phenotype. Here, we report the identification of the RNA-binding protein HuR/ELAVL1 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. HuR was found to be highly elevated and bound to a multitude of cancer-associated transcripts in human MPNST samples. Accordingly, genetic and pharmacological inhibition of HuR had potent cytostatic and cytotoxic effects on tumour growth, and strongly supressed metastatic capacity in vivo. Importantly, we linked the profound tumorigenic function of HuR to its ability to simultaneously regulate multiple essential oncogenic pathways in MPNST cells, including the Wnt/beta-Catenin, YAP/TAZ, Rb-E2F and BET proteins, which converge on key transcriptional networks. Given the exceptional dependency of MPNST cells on HuR for survival, proliferation, and dissemination, we propose that HuR represents a promising therapeutic target for MPNST treatment.
| Type: | Article |
|---|---|
| Title: | HuR/ELAVL1 drives malignant peripheral nerve sheath tumour growth and metastasis. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1172/JCI130379 |
| Publisher version: | https://doi.org/10.1172/JCI130379 |
| Language: | English |
| Additional information: | This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10096536 |
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