Review Volume 11, Issue 23 pp 11770—11792

Cancer stem cells-driven tumor growth and immune escape: the Janus face of neurotrophins

Figure 1. Neurotrophins signaling pathways in cell survival and death. NGF binds TrkA and p75 in a trimeric complex and mediates proliferation, differentiation, and survival via activation of different pathways, like PI3K/AKT, Ras/MAPK and PLC-γ. Upon p75NTR homo-dimerization, NGF is also able to activate NF-κB or JNK, resulting in RIP2 and NRAGE/NRIF signalings, respectively. On the contrary, proneurotrophins, and proNGF in particular, complex with p75NTR and sortilin, leading to activation of pro-apoptotic pathways and cell death.