Loss of p53 drives neuron reprogramming in head and neck cancer.

ABSTRACT: The solid tumour microenvironment includes nerve fibres that arise from the peripheral nervous system^1,2. Recent work indicates that newly formed adrenergic nerve fibres promote tumour growth, but the origin of these nerves and the mechanism of their inception are unknown^1,3. Here, by comparing the transcriptomes of cancer-associated trigeminal sensory neurons with those of endogenous neurons in mouse models of oral cancer, we identified an adrenergic differentiation signature. We show that loss of TP53 leads to adrenergic transdifferentiation of tumour-associated sensory nerves through loss of the microRNA miR-34a. Tumour growth was inhibited by sensory denervation or pharmacological blockade of adrenergic receptors, but not by chemical sympathectomy of pre-existing

SUBMITTER: Amit M 

PROVIDER: S-EPMC9723538 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature