Preprint Article Version 1 This version is not peer-reviewed

NGF Induces Proliferation and Aggressiveness In Prostate Cancer Cells.

Version 1 : Received: 10 April 2019 / Approved: 11 April 2019 / Online: 11 April 2019 (12:55:18 CEST)

A peer-reviewed article of this Preprint also exists.

Di Donato, M.; Cernera, G.; Migliaccio, A.; Castoria, G. Nerve Growth Factor Induces Proliferation and Aggressiveness In Prostate Cancer Cells. Cancers 2019, 11, 784. Di Donato, M.; Cernera, G.; Migliaccio, A.; Castoria, G. Nerve Growth Factor Induces Proliferation and Aggressiveness In Prostate Cancer Cells. Cancers 2019, 11, 784.

Journal reference: Cancers 2019, 11, 784
DOI: 10.3390/cancers11060784

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 effect. Nevertheless, PC gradually develops resistance, relapses and spreads. Most patients develop, indeed, castrate-resistant PC (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, TrkA. NGF signaling is deregulated in PC. In androgen-dependent PC cells, TrkA mediates the proliferative action of NGF through its cross talk 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-mesenchyme 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.

Subject Areas

NGF/TrkA signaling; mitogenesis; invasiveness; EMT; 3D models; castrate-resistant prostate cancers

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