Pro-nerve growth factor induces autocrine stimulation of breast cancer cell invasion through TRKA and sortilin.

The precursor of nerve growth factor (proNGF) has been described as a biologically active polypeptide able to induce apoptosis in neuronal cells, via the neurotrophin receptor p75NTR and the sortilin receptor. Herein, it is shown that proNGF is produced and secreted by breast cancer cells, stimulating their invasion. Using Western-blotting and mass spectrometry, proNGF was detected in a panel of breast cancer cells as well as in their conditioned media. Immunohistochemical analysis indicated an overproduction of proNGF in breast tumors, when compared with benign and normal breast biopsies, and a relationship to lymph node invasion in ductal carcinomas. Interestingly, siRNA against proNGF induced a decrease of breast cancer cell invasion that was restored by the addition of non-cleavable proNGF. The activation of TrkA, Akt, and Src, but not the MAP-kinases, was observed. In addition, the proNGF invasive effect was inhibited by the Trk pharmacological inhibitor K252a, a kinase-dead TrkA, and siRNA against TrkA sortilin, neurotensin, whereas siRNA against p75NTR and the MAP-kinase inhibitor PD98059 had no impact. These data reveal the existence of an autocrine loop stimulated by proNGF and mediated by TrkA and sortilin, with the activation of Akt and Src, for the stimulation of breast cancer cell invasion.

J. Biol. Chem.2011 Nov 29,.

Protein Name:pro-NGF
Gene Name:NGF NGFB


Recombinant Human ProNGF/NGF Pro Form
(CatNo. C078)

Recombinant Human precursor form of Nerve Growth Factor/pro-NGF produced in E. coli is a non-glycosylated non-covalently linked homodimer with each polypeptide chain containing 222 amino acids with an extra N-terminal Met with a molecular mass of 25kD.

The precursor form of the nerve growth factor (proNGF) like its mature form is characterized by the cystin knot motif consisting of three cystine bridges, whereas proneurotrophins and mature neurotrophins elicit opposite biological effects. ProNGF functions preferentially via the complex of pan-neurotrophin receptor p75 (p75NTR) and vps10p domain-containing receptor sortilin inducing neuronal apoptosis and contributing to age- and disease-related neurodegeneration.