Nerve growth factor receptor (CD271) (CD271)

The nerve growth factor receptor (NGFR), commonly known as CD271 or p75NTR, is a type I transmembrane receptor in the TNF receptor superfamily that binds neurotrophins such as NGF, BDNF, NT3, and NT4 with low affinity. It features an extracellular domain with four cysteine-rich repeats and an intracellular death domain that enables dual signaling: pro-survival pathways through interactions with tyrosine kinase receptors (e.g., TrkA) promoting cell proliferation, migration, axonal growth, and synaptic plasticity, or pro-apoptotic signaling in their absence. Expressed on neurons, melanocytes, and various cancer cells, NGFR regulates neuronal development and acts as a melanoma stem cell marker. In oncology, elevated NGFR expression drives malignancy in cancers like head and neck squamous cell carcinoma, bladder cancer, and melanoma by enhancing proliferation, stemness, migration, and resistance to therapies like cisplatin via mechanisms including mRNA noncoding functions with hnRNPA2B1. Its role as a poor prognostic biomarker highlights therapeutic potential, though targeting challenges arise from its context-dependent signaling switch between survival and death.

Other names

p75NTRlow-affinity nerve growth factor receptorNGFRTNFRSF16p75LNGFR

Inhibition of CD271-Rho GDI interaction reduces migration; CD271 knockdown induces apoptosis and impairs proliferation via E2F- and Myc-related pathways; interaction with tyrosine kinase receptors induces survival signaling, while death domain induces apoptosis