Fig. 2. Two direct ways of communication between tumor cells and nerves.

Tumors release molecules also secreted by nerves, including neurotropic factors, axon guidance molecules, and neurotransmitters. These factors act on receptors of nerves to drive the nerve reprogramming, while they can also act on tumor receptors to activate downstream signaling. In addition to the paracrine model, tumors and nerves can form the synapses for depolarization to promote tumor progression. TrkA tyrosine kinase receptor A, TrkB tyrosine kinase receptor B, NGFR nerve growth factor receptor, AchR acetylcholine receptor, ADRβ adrenoceptor β receptor, CX3CR1 C-X3-C motif chemokine receptor 1, GFR glial cell-derived neurotrophic factor family receptor.