Fig. 4
From: Chronic stress in solid tumor development: from mechanisms to interventions
The biological mechanism of chronic stress affecting perineural nerve of tumor. Chronic stress-induced ADRB increases BDNF via ADRB3/cAMP/EpAC/JNK and NGF via ADRB2/CREB or ADRB2/ERK. BDNF and NGF bind to TrkB in peritumor sensory neurons, promoting innervation of the tumor microenvironment and producing a sustained accumulation of adrenergic signals, forming a feed-forward loop. Chronic stress-induced low p53 in tumor cells leads to miR-34a loss in exosomes, resulting in increased ASCL1 in peritumor sensory neurons, which redifferentiates peritumor sensory neurons into adrenergic neurons. In addition, tumor cells secrete exosomes containing EphrinB1 into peritumor sensory nerves, inducing tumor innervation