Neurotrophin Signaling in Medulloblastoma

Author:

Thomaz Amanda,Jaeger Mariane,Brunetto Algemir L.,Brunetto André T.,Gregianin LauroORCID,de Farias Caroline BrunettoORCID,Ramaswamy Vijay,Nör Carolina,Taylor Michael D.,Roesler Rafael

Abstract

Neurotrophins are a family of secreted proteins that act by binding to tropomyosin receptor kinase (Trk) or p75NTR receptors to regulate nervous system development and plasticity. Increasing evidence indicates that neurotrophins and their receptors in cancer cells play a role in tumor growth and resistance to treatment. In this review, we summarize evidence indicating that neurotrophin signaling influences medulloblastoma (MB), the most common type of malignant brain cancer afflicting children. We discuss the potential of neurotrophin receptors as new therapeutic targets for the treatment of MB. Overall, activation of TrkA and TrkC types of receptors seem to promote cell death, whereas TrkB might stimulate MB growth, and TrkB inhibition displays antitumor effects. Importantly, we show analyses of the gene expression profile of neurotrophins and their receptors in MB primary tumors, which indicate, among other findings, that higher levels of NTRK1 or NTRK2 are associated with reduced overall survival (OS) of patients with SHH MB tumors.

Funder

National Council for Scientific and Technological Development

Rio Grande do Sul State Research Foundation

Coordination for the Improvement of Higher Education Personnel

Brain Tumour Foundation of Canada

American Brain Tumor Association

National Institutes of Health

Pediatric Brain Tumor Foundation

Terry Fox Research Institute

Canadian Institutes of Health Research

Genome Canada

Genome British Columbia

Ontario Institute for Cancer Research

Canadian Cancer Society Research Institute

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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