https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21423 NTR death receptor. Preclinical studies have shown that targeting neurotrophins and their receptors induce an inhibition of breast cancer cell survival, proliferation and invasion. Furthermore, targeting neurotrophins may also decrease tumor-induced cancer pain and this additional effect further strengthens their clinical relevance.]]> Sat 24 Mar 2018 08:05:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26338 NTR, sortilin) that can interact with the Trks and affect their activity. The Trks are predominantly expressed in nervous tissues, where they are essential for the growth, development, and maintenance of select types of both peripheral and central neurons and are involved in neurodegenerative diseases. The Trks are also found in some nonneuronal tissues and in a wide variety of tumors, where they can play an active role in tumor progression and metastasis. The activated Trk receptors primarily bind and signal through Shc, FRS2, and PLCᵧ, which in turn activate PI3K, the Erks, and the hydrolysis of inositol phospholipids, among other events, leading to the modulation of gene transcription.]]> Sat 24 Mar 2018 07:35:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22251 NTR 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 p75^NTR 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.]]> Sat 24 Mar 2018 07:17:32 AEDT ]]>