Nerve Growth Factor Induces Proliferation and Aggressiveness In Prostate Cancer Cells.
3D models
EMT
Keywords NGF/TrkA signaling
castrate-resistant prostate cancers
invasiveness
mitogenesis
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
06 Jun 2019
06 Jun 2019
Historique:
received:
10
04
2019
revised:
05
06
2019
accepted:
06
06
2019
entrez:
9
6
2019
pubmed:
9
6
2019
medline:
9
6
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31174415
pii: cancers11060784
doi: 10.3390/cancers11060784
pmc: PMC6627659
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : P.R.I.N. 2015B7M39T_003 and P.R.I.N. 2017EKMFTN_002
Organisme : P.O.R - Regione Calabria
ID : Progetto Razionale
Organisme : Fondazione U. Veronesi
ID : Post Doc fellowship 2019
Déclaration de conflit d'intérêts
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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