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Open AccessArticle

Nerve Growth Factor Induces Proliferation and Aggressiveness in Prostate Cancer Cells

Department of Precision Medicine-University of Campania ‘L. Vanvitelli’-via L. De Crecchio, 7-80138 Naples, Italy
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Cancers 2019, 11(6), 784; https://doi.org/10.3390/cancers11060784
Received: 10 April 2019 / Revised: 5 June 2019 / Accepted: 6 June 2019 / Published: 6 June 2019
(This article belongs to the Special Issue Prostate Cancer: Past, Present, and Future)
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Abstract

Resistance to hormone therapy and disease progression is the major challenge in clinical management of prostate cancer (PC). Drugs currently used in PC therapy initially show a potent antitumor effects, but PC gradually develops resistance, relapses and spreads. Most patients who fail primary therapy and have recurrences eventually develop castration-resistant prostate cancer (CRPC), which is almost incurable. The nerve growth factor (NGF) acts on a variety of non-neuronal cells by activating the NGF tyrosine-kinase receptor, tropomyosin receptor kinase A (TrkA). NGF signaling is deregulated in PC. In androgen-dependent PC cells, TrkA mediates the proliferative action of NGF through its crosstalk with the androgen receptor (AR). Epithelial PC cells, however, acquire the ability to express NGF and TrkA, as the disease progresses, indicating a role for NGF/TrkA axis in PC progression and androgen-resistance. We here report that once activated by NGF, TrkA mediates proliferation, invasiveness and epithelial-mesenchymal transition (EMT) in various CRPC cells. NGF promotes organoid growth in 3D models of CRPC cells, and specific inhibition of TrkA impairs all these responses. Thus TrkA represents a new biomarker to target in CRPC. View Full-Text
Keywords: NGF/TrkA signaling; mitogenesis; invasiveness; EMT; 3D models; castrate-resistant prostate cancers NGF/TrkA signaling; mitogenesis; invasiveness; EMT; 3D models; castrate-resistant prostate cancers
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Di Donato, M.; Cernera, G.; Migliaccio, A.; Castoria, G. Nerve Growth Factor Induces Proliferation and Aggressiveness in Prostate Cancer Cells. Cancers 2019, 11, 784.

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